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Dendritic cell-mediated responses to secreted Cryptosporidium effectors promote parasite-specific CD8+ T cell responses Mucosal Immunol. (IF 8.0) Pub Date : 2024-03-18 Breanne E. Haskins, Jodi A. Gullicksrud, Bethan A. Wallbank, Jennifer E. Dumaine, Amandine Guérin, Ian S. Cohn, Keenan M. O'Dea, Ryan D. Pardy, Maria I. Merolle, Lindsey A. Shallberg, Emma N. Hunter, Jessica H. Byerly, Eleanor J. Smith, Gracyn Y. Buenconsejo, Briana I. McLeod, David A. Christian, Boris Striepen, Christopher A. Hunter
causes debilitating diarrheal disease in patients with primary and acquired defects in T cell function However, it has been a challenge to understand how this infection generates T cell responses and how they mediate parasite control. Here, was engineered to express a parasite effector protein (MEDLE-2) that contains the major histocompatibility complex-I restricted SIINFEKL epitope which is recognized
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PD-1 regulates ILC3-driven intestinal immunity and homeostasis Mucosal Immunol. (IF 8.0) Pub Date : 2024-03-16 Nicolas Jacquelot, Le Xiong, Wang H.J. Cao, Qiutong Huang, Huiyang Yu, Azin Sayad, Casey J.A. Anttila, Tracey M. Baldwin, Peter F. Hickey, Daniela Amann-Zalcenstein, Pamela S. Ohashi, Stephen L. Nutt, Gabrielle T. Belz, Cyril Seillet
Interleukin-(IL) 22 production by intestinal group 3 innate lymphoid cells (ILC3) is critical to maintain gut homeostasis. However, IL-22 needs to be tightly controlled; reduced IL-22 expression is associated with intestinal epithelial barrier defect while its overexpression promotes tumor development. Here, using a single-cell ribonucleic acid sequencing approach, we identified a core set of genes
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Pulmonary immune profiling reveals common inflammatory endotypes of childhood wheeze and suppurative lung disease Mucosal Immunol. (IF 8.0) Pub Date : 2024-03-16 Melanie R. Neeland, Liam Gubbels, Anson Tsz Chun Wong, Hannah Walker, Sarath C. Ranganathan, Shivanthan Shanthikumar
Suppurative lung disease and wheezing are common respiratory diseases of childhood, however, due to poor understanding of underlying pathobiology, there are limited treatment options and disease recurrence is common. We aimed to profile the pulmonary and systemic immune response in children with wheeze and chronic suppurative lung disease for identification of endotypes that can inform improved clinical
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TL1A priming induces a multi-cytokine Th9 cell phenotype that promotes robust allergic inflammation in murine models of asthma Mucosal Immunol. (IF 8.0) Pub Date : 2024-03-15 Michelle L. Niese, Abigail L. Pajulas, Cameron R. Rostron, Cherry C.L. Cheung, Maya S. Krishnan, Jilu Zhang, Anthony M. Cannon, Mark H. Kaplan
The T helper (Th)9 subset of T lymphocytes secretes the pleiotropic cytokine interleukin (IL)-9 which has functions in allergic airway disease, helminth infections, and tumor immunity. We and others have shown presence of Th cells that secrete IL-9 and type 2 cytokines in mouse and human allergic inflammation. However, the cytokines that promote a multi-cytokine secreting phenotype have not been defined
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IL-5 antagonism reverses priming and activation of eosinophils in severe eosinophilic asthma Mucosal Immunol. (IF 8.0) Pub Date : 2024-03-15 Jian Luo, Wentao Chen, Wei Liu, Shan Jiang, Yuan Ye, Rahul Shrimanker, Gareth Hynes, Paul Klenerman, Ian D. Pavord, Luzheng Xue
Eosinophils are key effector cells mediating airway inflammation and exacerbation in patients with severe eosinophilic asthma. They are present in increased number and activation state in the airway mucosa and lumen. Interleukin-5 (IL-5) is the key eosinophil growth factor that is thought to play a role in eosinophil priming and activation. However, the mechanism of these effects is still not fully
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Migratory CD103+CD11b+ cDC2 cells in Peyer’s patches are critical for gut IgA responses following oral immunization Mucosal Immunol. (IF 8.0) Pub Date : 2024-03-15 Inta Gribonika, Anneli Strömberg, Rakesh K. Chandode, Karin Schön, Katharina Lahl, Mats Bemark, Nils Lycke
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The bacterial lysate OM-85 engages Toll-like receptors 2 and 4 triggering an immunomodulatory gene signature in human myeloid cells Mucosal Immunol. (IF 8.0) Pub Date : 2024-03-04 Hanif J. Khameneh, Marco Bolis, Pedro M.O. Ventura, Giada A. Cassanmagnago, Berenice A. Fischer, Alessandro Zenobi, Jessica Guerra, Irene Buzzago, Maurizio Bernasconi, Guido J.R. Zaman, Andrea Rinaldi, Simone G. Moro, Federica Sallusto, Edouard Baulier, Christian Pasquali, Greta Guarda
OM-85 is a bacterial lysate used in clinical practice to reduce duration and frequency of recurrent respiratory tract infections. Whereas knowledge of its regulatory effects has substantially advanced, the mechanisms of OM-85 sensing remain inadequately addressed. Here, we show that the immune response to OM-85 in the mouse is largely mediated by myeloid immune cells through Toll-like receptor (TLR)
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Stress systems exacerbate the inflammatory response after corneal abrasion in sleep-deprived mice via the IL-17 signaling pathway Mucosal Immunol. (IF 8.0) Pub Date : 2024-02-28 Yunxia Xue, Pengyang Xu, Yu Hu, Sijing Liu, Ruyu Yan, Shutong Liu, Yan Li, Jun Liu, Ting Fu, Zhijie Li
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Epithelial regulation of microbiota-immune cell dynamics Mucosal Immunol. (IF 8.0) Pub Date : 2024-02-28 Bailey J. Didriksen, Emily M. Eshleman, Theresa Alenghat
The mammalian gastrointestinal tract hosts a diverse community of trillions of microorganisms, collectively termed the microbiota, which play a fundamental role in regulating tissue physiology and immunity. Recent studies have sought to dissect the cellular and molecular mechanisms mediating communication between the microbiota and host immune system. Epithelial cells line the intestine and form an
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Mechanotransduction-induced interplay between phospholamban and yes-activated protein induces smooth muscle cell hypertrophy Mucosal Immunol. (IF 8.0) Pub Date : 2024-02-27 Renee Rawson, Loan Duong, Eugene Tkachenko, Austin W.T. Chiang, Kevin Okamoto, Ranjan Dohil, Nathan E. Lewis, Richard Kurten, Edsel M. Abud, Seema S. Aceves
The gastrointestinal system is a hollow organ affected by fibrostenotic diseases that cause volumetric compromise of the lumen via smooth muscle hypertrophy and fibrosis. Many of the driving mechanisms remain unclear. Yes-associated protein-1 (YAP) is a critical mechanosensory transcriptional regulator that mediates cell hypertrophy in response to elevated extracellular rigidity. In the type 2 inflammatory
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Deficiency of immunoglobulin IgSF6 enhances antibacterial effects by promoting endoplasmic reticulum stress and the inflammatory response in intestinal macrophages Mucosal Immunol. (IF 8.0) Pub Date : 2024-02-21 Yuting Wu, Panrui Zhang, Tianlu Shi, Dan Cao, Wen Pan
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IL-1α is required for T cell-driven weight loss after respiratory viral infection Mucosal Immunol. (IF 8.0) Pub Date : 2024-02-19 Ziyin Wang, Leah F. Cuthbertson, Chubicka Thomas, Hadijatou J Sallah, Lucy G. Mosscrop, Haoyuan Li, Tiina Talts, Kartik Kumar, Miriam F. Moffatt, John S. Tregoning
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Intraepithelial lymphocytes promote intestinal regeneration through CD160/HVEM signaling Mucosal Immunol. (IF 8.0) Pub Date : 2024-02-08 Jiaoyan Huang, Xin Zhang, Hongkai Xu, Liuhui Fu, Yuke Liu, Jie Zhao, Jida Huang, Zuodong Song, Mingzhao Zhu, Yang-Xin Fu, Ye-Guang Chen, Xiaohuan Guo
Chemotherapy and radiotherapy frequently lead to intestinal damage. The mechanisms governing the repair or regeneration of intestinal damage are still not fully elucidated. Intraepithelial lymphocytes (IELs) are the primary immune cells residing in the intestinal epithelial layer. However, whether IELs are involved in intestinal epithelial injury repair remains unclear. Here, we found that IELs rapidly
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A Trefoil factor 3-Lingo2 axis restrains proliferative expansion of type-1 T helper cells during GI nematode infection Mucosal Immunol. (IF 8.0) Pub Date : 2024-02-08 Lucas M. Ethgen, Christopher Pastore, Cailu Lin, Danielle R Reed, Li-Yin Hung, Bonnie Douglas, Dominic Sinker, De'Broski R. Herbert, Nicole M. Belle
Host defense at the mucosal interface requires collaborative interactions between diverse cell lineages. Epithelial cells damaged by microbial invaders release reparative proteins such as the Trefoil factor family (TFF) peptides that functionally restore barrier integrity. However, whether TFF peptides and their receptors also serve instructive roles for immune cell function during infection is incompletely
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Salivary IgA and vimentin differentiate in vitro SARS-CoV-2 infection: a study of 290 convalescent COVID-19 patients. Mucosal Immunol. (IF 8.0) Pub Date : 2023-11-23 Samuel Ellis,Rosie Way,Miranda Nel,Alice Burleigh,Ivan Doykov,Japhette Kembou-Ringert,Maximillian Woodall,Tereza Masonou,Katie-Marie Case,Arturo Torres Ortez,Timothy D McHugh,Antonio Casal,Laura E McCoy,Sudaxshina Murdan,Robert E Hynds,Kimberly C Gilmour,Louis Grandjean,Mario Cortina-Borja,Wendy E Heywood,Kevin Mills,Claire M Smith
SARS-CoV-2 initially infects cells in the nasopharynx and oral cavity. The immune system at these mucosal sites plays a crucial role in minimizing viral transmission and infection. To develop new strategies for preventing SARS-CoV-2 infection, this study aimed to identify proteins that protect against viral infection in saliva. We collected 551 saliva samples from 290 healthcare workers who had tested
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Single-Cell Landscape Reveals the Epithelial Cell-Centric Proinflammatory Immune Microenvironment in Dry Eye Development. Mucosal Immunol. (IF 8.0) Pub Date : 2023-11-23 Zihao Liu,He Xie,Ling Li,Dan Jiang,Yuna Qian,Xinhao Zhu,Mali Dai,Yanxiao Li,Ruifen Wei,Zan Luo,Weihao Xu,Qinxiang Zheng,Jianliang Shen,Meng Zhou,Wenwen Zeng,Wei Chen
Dry eye disease (DED) is a prevalent chronic eye disease characterized by an aberrant inflammatory response in ocular surface mucosa. The immunological alterations underlying DED remain largely unknown. In this study, we employed single-cell transcriptome sequencing of conjunctival tissue from environment-induced DED mice to investigate multicellular ecosystem and functional changes at different DED
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Exploring the Oral-Gut Linkage: Interrelationship Between Oral and Systemic Diseases. Mucosal Immunol. (IF 8.0) Pub Date : 2023-11-23 Kyoko Yamazaki,Nobuhiko Kamada
The oral cavity harbors a diverse microbiota that plays a significant role in maintaining homeostasis. Disruption of this balance can lead to various oral diseases, including periodontitis. Accumulating evidence suggests a connection between periodontitis and extra-oral diseases such as cardiovascular disease, rheumatoid arthritis, obesity, and diabetes. During periodontitis, oral bacteria enter the
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A proinflammatory gut mucosal cytokine response is associated with mild COVID-19 disease and superior induction of serum antibodies. Mucosal Immunol. (IF 8.0) Pub Date : 2023-11-21 Dana Costigan,Joe Fenn,Sandi Yen,Nicholas Ilott,Samuel Bullers,Jessica Hale,William Greenhalf,Emily Conibear,Aleksandra Koycheva,Kieran Madon,Ishrat Jahan,Ming Huang,Anjna Badhan,Eleanor Parker,Carolina Rosadas,Kelsey Jones,Myra McClure,Richard Tedder,Graham Taylor,Kenneth J Baillie,Malcolm G Semple,Peter Jm Openshaw,Claire Pearson,Jethro Johnson,Ajit Lalvani,Emily E Thornton,,
The relationship between gastrointestinal tract infection, the host immune response and clinical outcome of disease is not well understood in COVID-19. We sought to understand the effect of intestinal immune responses to SARS-CoV-2 on patient outcomes including magnitude of systemic antibody induction. Combining two prospective cohort studies, ISARIC4C and INSTINCT, we acquired samples from 88 COVID-19
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Role reversals: non-canonical roles for immune and non-immune cells in the gut. Mucosal Immunol. (IF 8.0) Pub Date : 2023-11-13 Jacqueline L E Tearle,Adelynn Tang,Ajithkumar Vasanthakumar,Kylie R James
The intestine is home to an intertwined network of epithelial, immune, and neuronal cells as well as the microbiome, with implications for immunity, systemic metabolism, and behavior. While the complexity of this microenvironment has long since been acknowledged, recent technological advances have propelled our understanding to an unprecedented level. Notably, the microbiota and non-immune or structural
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Intestinal damage is required for the pro-inflammatory differentiation of commensal CBir1-specific T cells. Mucosal Immunol. (IF 8.0) Pub Date : 2023-11-10 Chiara Sorini,Rebeca F Cardoso,Kumar P Tripathi,Jeff E Mold,Oscar E Diaz,Yael Holender,Bianca C Kern,Paulo Czarnewski,Nicola Gagliani,Eduardo J Villablanca
Commensal-specific clusters of differentiation (CD)4+ T cells are expanded in patients with inflammatory bowel disease (IBD) compared to healthy individuals. How and where commensal-specific CD4+ T cells get activated is yet to be fully understood. We used CBir1 TCR-transgenic CD4+ T cells, specific to a commensal bacterial antigen, and different mouse models of IBD to characterize the dynamics of
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Bi-directional signalling between the intestinal epithelium and type-3 innate lymphoid cells (ILC3) regulates secretory dynamics and IL-22. Mucosal Immunol. (IF 8.0) Pub Date : 2023-11-10 Emily Read,Ainize Peña-Cearra,Diana Coman,Geraldine M Jowett,Matthew W H Chung,Isabelle Coales,Sofia Syntaka,Rachel E Finlay,Roser Tachó-Piñot,Sjoerd van Der Post,Umar Naizi,Luke B Roberts,Matthew R Hepworth,Michael A Curtis,Joana F Neves
Type-3 innate lymphoid cells (ILC3) respond to localised environmental cues to regulate homeostasis and orchestrate immunity in the intestine. The intestinal epithelium is an important upstream regulator and downstream target of ILC3 signalling, however the complexity of mucosal tissues can hinder efforts to define specific interactions between these two compartments. Here, we employ a reductionist
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Heat shock factor 1 drives regulatory T cell induction to limit murine intestinal inflammation. Mucosal Immunol. (IF 8.0) Pub Date : 2023-11-07 Colm B Collins,Tom T Nguyen,Robert S Leddy,Kibrom M Alula,Alyson R Yeckes,Derek Strassheim,Carol M Aherne,Marisa E Luck,Vijaya Karoor,Paul Jedlicka,Ansen Pierce,Edwin F de Zoeten
The heat shock response is a critical component of the inflammatory cascade that prevents misfolding of new proteins and regulates immune responses. Activation of CD4+ T cells causes an upregulation of heat shock transcription factor, heat shock factor 1 (HSF1). We hypothesized that HSF1 promotes a pro-regulatory phenotype during inflammation. To validate this hypothesis, we interrogated cell-specific
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B cell-mediated CD4 T-cell costimulation via CD86 exacerbates pro-inflammatory cytokine production during autoimmune intestinal inflammation. Mucosal Immunol. (IF 8.0) Pub Date : 2023-10-31 Iana Gadjalova,Julia M Heinze,Marie C Goess,Julian Hofmann,Annalisa Buck,Marie-Christin Weber,Birgit Blissenbach,Maximilian Kampick,Oleg Krut,Katja Steiger,Klaus-Peter Janssen,Philipp-Alexander Neumann,Jürgen Ruland,Selina J Keppler
Dysregulated B cell responses have been described in inflammatory bowel disease (IBD) patients; however, the role of B cells in IBD pathology remained incompletely understood. We here provide evidence for the detrimental role of activated B cells during the onset of autoimmune intestinal inflammation. Using Wiskott-Aldrich Syndrome interacting protein deficient (Wipf1-/-) mice as a mouse model of chronic
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The menstrual cycle regulates migratory CD4 T-cell surveillance in the female reproductive tract via CCR5 signaling. Mucosal Immunol. (IF 8.0) Pub Date : 2023-10-20 M Elliott Williams,Felica P Hardnett,Anandi N Sheth,Alexander N Wein,Zheng-Rong Tiger Li,Jessica Radzio-Basu,Chuong Dinh,Lisa B Haddad,Elizabeth M B Collins,Igho Ofotokun,Rustom Antia,Christopher D Scharer,J Gerardo Garcia-Lerma,Jacob E Kohlmeier,Alison Swaims-Kohlmeier
Despite their importance for immunity against sexually transmitted infections, the composition of female reproductive tract (FRT) memory T-cell populations in response to changes within the local tissue environment under the regulation of the menstrual cycle remains poorly defined. Here, we show that in humans and pig-tailed macaques, the cycle determines distinct clusters of differentiation 4 T-cell
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Intestinal immunological events of acute and resolved SARS-CoV-2 infection in non-human primates. Mucosal Immunol. (IF 8.0) Pub Date : 2023-10-10 Stéphane Hua,Krishna Latha,Romain Marlin,Keltouma Benmeziane,Laetitia Bossevot,Sébastien Langlois,Francis Relouzat,Nathalie Dereuddre-Bosquet,Roger Le Grand,Mariangela Cavarelli
SARS-CoV-2 infection has been associated with intestinal mucosa barrier damage, leading to microbial and endotoxin translocation, heightened inflammatory responses, and aggravated disease outcomes. This study aimed to investigate the immunological mechanisms associated with impaired intestinal barrier function. We conducted a comprehensive analysis of gut damage and inflammation markers, and phenotypic
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Acrylamide, an air pollutant, enhances allergen-induced eosinophilic lung inflammation via group 2 innate lymphoid cells. Mucosal Immunol. (IF 8.0) Pub Date : 2023-10-05 Hsiang-Han Su,Chih-Mei Cheng,Yung-Ning Yang,Yu-Wei Chang,Chia-Yang Li,Shin-Ting Wu,Chia-Chi Lin,Hsin-En Wu,Jau-Ling Suen
Air pollution significantly impacts the aggravation of asthma. Exposure to acrylamide, a volatile organic compound in tobacco smoke, is associated with elevated risks of allergy-related outcomes among active smokers. As group 2 innate lymphoid cells (ILC2s) can act as an environmental sensor and significantly contribute to protease allergen-induced lung inflammation, we aimed to elucidate the causal
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The IL-17A-neutrophil axis promotes epithelial cell IL-33 production during nematode lung migration. Mucosal Immunol. (IF 8.0) Pub Date : 2023-09-30 Jesuthas Ajendra,Pedro H Papotto,James E Parkinson,Rebecca J Dodd,André L Bombeiro,Stella Pearson,Brian H K Chan,Julie C Ribot,Henry J McSorley,Tara E Sutherland,Judith E Allen
The early migratory phase of pulmonary helminth infections is characterized by tissue injury leading to the release of the alarmin IL-33 and subsequent induction of type 2 immune responses. We recently described a role for IL-17A, through suppression of IFNγ, as an important inducer of type 2 responses during infection with the lung-migrating rodent nematode Nippostrongylus brasiliensis. Here, we aimed
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Bcl-6 expression by CD4+ T cells determines concomitant immunity and host resistance across distinct parasitic infections. Mucosal Immunol. (IF 8.0) Pub Date : 2023-09-19 Alexandre P Meli,Gabriel A Russell,Sharada Swaminathan,Laura Weichselbaum,Clara A MacMahon,Erwan Pernet,Danielle Karo-Atar,Dakota Rogers,Annie Rochette,Ghislaine Fontes,Judith N Mandl,Maziar Divangahi,Ophir D Klein,Alex Gregorieff,Simona Stäger,Irah L King
Cluster of differentiation (CD4+) T cells consist of multiple subtypes, defined by expression of lineage-specific transcription factors, that contribute to the control of infectious diseases by providing help to immune and nonimmune target cells. In the current study, we examined the role of B cell lymphoma (Bcl)-6, a transcriptional repressor and master regulator of T follicular helper cell differentiation
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Obesity amplifies influenza virus-driven disease severity in male and female mice. Mucosal Immunol. (IF 8.0) Pub Date : 2023-09-18 Pablo C Alarcon,Michelle S M A Damen,Cassidy J Ulanowicz,Keisuke Sawada,Jarren R Oates,Andrea Toth,Jennifer L Wayland,Hak Chung,Traci E Stankiewicz,Maria E Moreno-Fernandez,Sara Szabo,William J Zacharias,Senad Divanovic
Influenza virus-induced respiratory pneumonia remains a major public health concern. Obesity, metabolic diseases, and female sex are viewed as independent risk factors for worsened influenza virus-induced lung disease severity. However, lack of experimental models of severe obesity in female mice limits discovery-based studies. Here, via utility of thermoneutral housing (30 °C) and high-fat diet (HFD)
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Alpha-tocopherylquinone-mediated activation of the Aryl Hydrocarbon Receptor regulates the production of inflammation-inducing cytokines and ameliorates intestinal inflammation. Mucosal Immunol. (IF 8.0) Pub Date : 2023-09-15 Kushal Saha,Ashwinkumar Subramenium Ganapathy,Alexandra Wang,Priya Arumugam,Nathan Michael Morris,Leonard Harris,Gregory Yochum,Walter Koltun,Gary H Perdew,Meghali Nighot,Thomas Ma,Prashant Nighot
This study investigated the role of Alpha-tocopherylquinone (TQ) in regulating the intestinal immune system and the underlying mechanisms. In the experimental dextran sodium sulfate and T cell-mediated colitis models, TQ significantly reduced the mRNA levels of interleukin (IL)-6, IL-1β, IL-17A, IL-23, and tumor necrosis factor (TNF)-α and the abundance of proinflammatory macrophages, T helper (Th)17
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GL7 ligand expression defines a novel subset of CD4+ TRM cells in lungs recovered from pneumococcus. Mucosal Immunol. (IF 8.0) Pub Date : 2023-09-14 Carolina Lyon De Ana,Anukul T Shenoy,Kimberly A Barker,Emad I Arafa,Neelou S Etesami,Filiz T Korkmaz,Alicia M Soucy,Michael P Breen,Ian M C Martin,Brian R Tilton,Priyadharshini Devarajan,Nicholas A Crossland,Riley M F Pihl,Wesley N Goltry,Anna C Belkina,Matthew R Jones,Lee J Quinton,Joseph P Mizgerd
Streptococcus pneumoniae is the most common etiology of bacterial pneumonia, one of the leading causes of death in children and the elderly worldwide. During non-lethal infections with S. pneumoniae, lymphocytes accumulate in the lungs and protect against reinfection with serotype-mismatched strains. Cluster of differentiation CD4+ resident memory T (TRM) cells are known to be crucial for this protection
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LAIR-1 limits macrophage activation in acute inflammatory lung injury. Mucosal Immunol. (IF 8.0) Pub Date : 2023-09-09 Doumet Georges Helou,Christine Quach,Benjamin P Hurrell,Xin Li,Meng Li,Amitis Akbari,Stephen Shen,Pedram Shafiei-Jahani,Omid Akbari
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious health problems that manifest as acute respiratory failure in response to different conditions, including viral respiratory infections. Recently, the inhibitory properties of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) were demonstrated in allergic and viral airway inflammation. In this study, we investigate
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Understanding the molecular mechanisms of anti-trafficking therapies and their clinical relevance in inflammatory bowel disease. Mucosal Immunol. (IF 8.0) Pub Date : 2023-09-03 Saurabh Mehandru,Jean-Frederic Colombel,Julius Juarez,James Bugni,James O Lindsay
In patients with inflammatory bowel disease (IBD), a combination of dysbiosis, increased intestinal permeability, and insufficient regulatory responses facilitate the development of chronic inflammation, which is driven by a complex interplay between the mucosal immune system and the environment and sustained by immune priming and ongoing cellular recruitment to the gut. The localization of immune
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Shining the spotlight on urinary tract immunology. Mucosal Immunol. (IF 8.0) Pub Date : 2023-09-01 Theresa T H Nguyen,Malcolm R Starkey
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Age-differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - Effects of vitamin D. Mucosal Immunol. (IF 8.0) Pub Date : 2023-09-01 Francesca Sposito,Shaun H Pennington,Christopher A W David,Jack Duggan,Sarah Northey,Giancarlo A Biagini,Neill J Liptrott,Amandine Charras,Paul S McNamara,Christian M Hedrich
Young age and high vitamin D plasma levels have been associated with lower SARS-CoV-2 infection risk and favourable disease outcomes. This study investigated mechanisms associated with differential responses to SARS-CoV-2 across age groups and effects of vitamin D. Nasal epithelia were collected from healthy children and adults and cultured for four weeks at the air-liquid interface with and without
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Stem cell factor inhibition reduces Th2 inflammation and cellular infiltration in a mouse model of eosinophilic esophagitis. Mucosal Immunol. (IF 8.0) Pub Date : 2023-08-21 Catherine Ptaschinski,Diana Zhu,Wendy Fonseca,Nicholas W Lukacs
Eosinophilic esophagitis (EoE) is a T helper (Th)2-mediated inflammatory disorder characterized endoscopically by eosinophilic infiltration leading to fibrosis of the esophagus. Stem cell factor (SCF), a multifunctional cytokine, is upregulated in several allergic diseases, including in patients with EoE. Mast cells and eosinophils express c-kit, the cell surface receptor for SCF, and have been found
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Airway epithelium IgE-FcεRI cross-link induces epithelial barrier disruption in severe T2-high asthma. Mucosal Immunol. (IF 8.0) Pub Date : 2023-08-16 Chih-Ming Weng,Meng-Jung Lee,Wei Chao,Yuh-Rong Lin,Chun-Ju Chou,Mei-Chuan Chen,Chun-Liang Chou,I-Lin Tsai,Chien-Huang Lin,Kian Fan Chung,Han-Pin Kuo
Although high-affinity immunoglobulin (Ig)E receptor (FcεRI) expression is upregulated in type 2 (T2)-high asthmatic airway epithelium, its functional role in airway epithelial dysfunction has not been elucidated. Here we report the upregulated expression of FcεRI and p-EGFR (Epidermal Growth Factor Receptor), associated with decreased expression of E-cadherin and claudin-18 in bronchial biopsies of
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Increased innate immune activation induces protective RSV-specific lung-resident memory T cells in neonatal mice. Mucosal Immunol. (IF 8.0) Pub Date : 2023-07-21 Allison M W Malloy,Zhongyan Lu,Margaret Kehl,Jarina Pena DaMata,Annie W Lau-Kilby,Mathilde Turfkruyer
Young infants frequently experience respiratory tract infections, yet vaccines designed to provide mucosal protection are lacking. Localizing pathogen-specific cellular and humoral immune responses to the lung could provide improved immune protection. We used a well-characterized murine model of respiratory syncytial virus (RSV) to study the development of lung-resident memory T cells (TRM) in neonatal
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Metabolic adaption of mucosal macrophages: Is metabolism a driver of persistence across tissues? Mucosal Immunol. (IF 8.0) Pub Date : 2023-07-15 Clare L Bennett,Georgia Perona-Wright
Macrophages play essential roles in tissue homeostasis, defense, and repair. Their functions are highly tissue-specific, and when damage and inflammation stimulate repopulation by circulating monocytes, the incoming monocytes rapidly acquire the same, tissue-specific functions as the previous, resident macrophages. Several environmental factors are thought to guide the functional differentiation of
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Sialylation shapes mucus architecture inhibiting bacterial invasion in the colon. Mucosal Immunol. (IF 8.0) Pub Date : 2023-07-13 Mugen Taniguchi,Ryu Okumura,Takahisa Matsuzaki,Ayaka Nakatani,Kei Sakaki,Shota Okamoto,Airi Ishibashi,Haruka Tani,Momoka Horikiri,Naritaka Kobayashi,Hiroshi Y Yoshikawa,Daisuke Motooka,Daisuke Okuzaki,Shota Nakamura,Toshiyuki Kida,Akihiko Kameyama,Kiyoshi Takeda
In the intestine, mucin 2 (Muc2) forms a network structure and prevents bacterial invasion. Glycans are indispensable for Muc2 barrier function. Among various glycosylation patterns of Muc2, sialylation inhibits bacteria-dependent Muc2 degradation. However, the mechanisms by which Muc2 creates the network structure and sialylation prevents mucin degradation remain unknown. Here, by focusing on two
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Role of MAIT cells in gastrointestinal tract bacterial infections in humans: More than a gut feeling. Mucosal Immunol. (IF 8.0) Pub Date : 2023-06-21 Yichao Zheng,Fei Han,Amanda Ho,Yiting Xue,Zhengyu Wu,Xingchi Chen,Johan K Sandberg,Shaohua Ma,Edwin Leeansyah
Mucosa-associated invariant T (MAIT) cells are the largest population of unconventional T cells in humans. These antimicrobial T cells are poised with rapid effector responses following recognition of the cognate riboflavin (vitamin B2)-like metabolite antigens derived from microbial riboflavin biosynthetic pathway. Presentation of this unique class of small molecule metabolite antigens is mediated
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Determination of Tr1 cell populations correlating with distinct activation states in acute IAV infection. Mucosal Immunol. (IF 8.0) Pub Date : 2023-06-14 Caitlin A Abbott,Emily L Freimayer,Timona S Tyllis,Todd S Norton,Mohammed Alsharifi,Aaron H S Heng,Stephen M Pederson,Zhipeng Qu,Mark Armstrong,Geoffrey R Hill,Shaun R McColl,Iain Comerford
Type I regulatory (Tr1) cells are defined as FOXP3-IL-10-secreting clusters of differentiation (CD4+) T cells that contribute to immune suppression and typically express the markers LAG-3 and CD49b and other co-inhibitory receptors. These cells have not been studied in detail in the context of the resolution of acute infection in the lung. Here, we identify FOXP3- interleukin (IL)-10+ CD4+ T cells
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Sex-associated early-life viral innate immune response is transcriptionally associated with chromatin remodeling of type-I IFN-inducible genes. Mucosal Immunol. (IF 8.0) Pub Date : 2023-06-10 Carrie-Anne Malinczak,Wendy Fonseca,Mohamed M Mire,Abhijit Parolia,Arul Chinnaiyan,Andrew J Rasky,Susan Morris,Kazuma Yagi,Jennifer R Bermick,Nicholas W Lukacs
This study investigates sex-associated systemic innate immune differences by examining bone marrow-derived dendritic cells (BMDCs). BMDC grown from 7-day-old mice show enhanced type-I interferon (IFN) signaling in female compared to male BMDC. Upon respiratory syncytial virus (RSV) infection of 7-day-old mice, a significantly altered phenotype of BMDC at 4 weeks post-infection is observed in a sex-dependent
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Obesity-induced hyperglycemia impairs oral tolerance induction and aggravates food allergy. Mucosal Immunol. (IF 8.0) Pub Date : 2023-06-10 Lícia Torres,Mariana Camila Gonçalves Miranda,Vinícius Dantas Martins,Felipe Caixeta,Mariana de Almeida Oliveira,Luísa Martins Trindade,Helder Carvalho de Assis,Valbert Nascimento,Natália Pinheiro Rosa,Eliane Gomes,Sophia Oliveira Almeida,Florian Marquet,Laurent Genser,Genevieve Marcelin,Karine Clément,Momtchilo Russo,Ana Maria Caetano Faria,Tatiani Uceli Maioli
Obesity and type 2 diabetes (T2D) have been found to be associated with abnormalities in several organs, including the intestine. These conditions can lead to changes in gut homeostasis, compromising tolerance to luminal antigens and increasing susceptibility to food allergies. The underlying mechanisms for this phenomenon are not yet fully understood. In this study, we investigated changes in the
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Mast cells disrupt the function of the esophageal epithelial barrier. Mucosal Immunol. (IF 8.0) Pub Date : 2023-06-10 Mirelle T A Kleuskens,Marie K Bek,Youmna Al Halabi,Bart R J Blokhuis,Mara A P Diks,Maria L Haasnoot,Johan Garssen,Albert J Bredenoord,Betty C A M van Esch,Frank A Redegeld
Mast cells (MCs) accumulate in the epithelium of patients with eosinophilic esophagitis (EoE), an inflammatory disorder characterized by extensive esophageal eosinophilic infiltration. Esophageal barrier dysfunction plays an important role in the pathophysiology of EoE. We hypothesized that MCs contribute to the observed impaired esophageal epithelial barrier. Herein, we demonstrate that coculture
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Indoleamine 2,3-dioxygenase 1 regulates cell permissivity to astrovirus infection. Mucosal Immunol. (IF 8.0) Pub Date : 2023-06-07 Valerie Cortez,Brandi Livingston,Bridgett Sharp,Virginia Hargest,James B Papizan,Natalie Pedicino,Sarah Lanning,Summer Vaughn Jordan,Jacob Gulman,Peter Vogel,Rebecca M DuBois,Jeremy Chase Crawford,David F Boyd,Shondra M Pruett-Miller,Paul G Thomas,Stacey Schultz-Cherry
Astroviruses cause a spectrum of diseases spanning asymptomatic infections to severe diarrhea, but little is understood about their pathogenesis. We previously determined that small intestinal goblet cells were the main cell type infected by murine astrovirus-1. Here, we focused on the host immune response to infection and inadvertently discovered a role for indoleamine 2,3-dioxygenase 1 (Ido1), a
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Expanding the role of MHC class II on intestinal epithelial cells. Mucosal Immunol. (IF 8.0) Pub Date : 2023-06-05 Markus B Geuking
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Peyer's patch phagocytes acquire specific transcriptional programs that influence their maturation and activation profiles. Mucosal Immunol. (IF 8.0) Pub Date : 2023-05-29 Cynthia Arroyo Portilla,Romain Fenouil,Camille Wagner,Cécilia Luciani,Margaux Lagier,Clément Da Silva,Fanny Hidalgo-Villeda,Lionel Spinelli,Mathieu Fallet,Julie Tomas,Jean-Pierre Gorvel,Hugues Lelouard
Peyer's patches (PPs) are secondary lymphoid organs in contact with the external environment via the intestinal lumen, thus combining antigen sampling and immune response initiation sites. Therefore, they provide a unique opportunity to study the entire process of phagocyte differentiation and activation in vivo. Here, we deciphered the transcriptional and spatial landscape of PP phagocyte populations
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Expansion of MAIT cells in the combined absence of NKT and γδ-T cells. Mucosal Immunol. (IF 8.0) Pub Date : 2023-05-13 Calvin Xu,Shihan Li,Thomas S Fulford,Susan N Christo,Laura K Mackay,Daniel Hd Gray,Adam P Uldrich,Daniel G Pellicci,Dale I Godfrey,Hui-Fern Koay
Mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, and γδT cells are collectively referred to as 'unconventional T cells' due to their recognition of non-peptide antigens and restriction to MHC-I-like molecules. However, the factors controlling their widely variable frequencies between individuals and organs are poorly understood. We demonstrated that MAIT cells are increased
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IL-18 is required for the TH1-adaptation of TREG cells and the selective suppression of TH17 responses in acute and chronic infections. Mucosal Immunol. (IF 8.0) Pub Date : 2023-05-13 Fernando Alvarez,Roman Istomine,Alonso Da Silva Lira Filho,Tho-Alfakar Al-Aubodah,Daniel Huang,Rakan Okde,Martin Olivier,Jörg H Fritz,Ciriaco A Piccirillo
Interleukin (IL)-18, a member of the IL-1 family of alarmins, is abundantly released in the lungs following influenza A (IAV) infections yet its role in orchestrating the local adaptive immune response remains ill defined. Through genetic disruption of the IL-18 receptor, we demonstrate that IL-18 not only promotes pulmonary TH1 responses but also influences regulatory T cells (TREG) function in the
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Butyrate regulates neutrophil homeostasis and impairs early antimicrobial activity in the lung. Mucosal Immunol. (IF 8.0) Pub Date : 2023-05-12 Anh Thu Dang,Christina Begka,Céline Pattaroni,Laura R Caley,R Andres Floto,Daniel G Peckham,Benjamin J Marsland
Short-chain fatty acids (SCFAs) are metabolites that are produced after microbial fermentation of dietary fiber and impact cell metabolism and anti-inflammatory pathways both locally in the gut and systemically. In preclinical models, administration of SCFAs, such as butyrate, ameliorates a range of inflammatory disease models including allergic airway inflammation, atopic dermatitis, and influenza
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Interleukin-9 promotes mast cell progenitor proliferation and CCR2-dependent mast cell migration in allergic airway inflammation. Mucosal Immunol. (IF 8.0) Pub Date : 2023-05-11 Abigail Pajulas,Yongyao Fu,Cherry C L Cheung,Michelle Chu,Anthony Cannon,Nada Alakhras,Jilu Zhang,Benjamin J Ulrich,Andrew S Nelson,Baohua Zhou,Mark H Kaplan
Allergic asthma is a chronic lung disease characterized by airway hyperresponsiveness and cellular infiltration that is exacerbated by immunoglobulin E-dependent mast cell (MC) activation. Interleukin-9 (IL-9) promotes MC expansion during allergic inflammation but precisely how IL-9 expands tissue MCs and promotes MC function is unclear. In this report, using multiple models of allergic airway inflammation
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A2Ar-dependent PD-1+ and TIGIT+ Treg cells have distinct homing requirements to suppress autoimmune uveitis in mice. Mucosal Immunol. (IF 8.0) Pub Date : 2023-05-09 Kayleigh Peters,Trisha McDonald,Fauziyya Muhammad,Marisa Walsh,Kayla Drenen,Alyssa Montieth,C Stephen Foster,Darren J Lee
The proper function of regulatory T cells (Tregs) to suppress inflammation requires homing to the correct tissue site. Resolution of autoimmune uveitis generates distinct programmed death receptor 1 (PD-1+) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT+) Tregs in an adenosine 2A receptor (A2Ar)-dependent manner found in the spleen. Where
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Expanded ILC2s in human infant intestines promote tissue growth. Mucosal Immunol. (IF 8.0) Pub Date : 2023-04-29 Kimberly J Möller,Lucy H M Wegner,Jakob Malsy,Martin E Baumdick,Malte Borggrewe,Ana Jordan-Paiz,Johannes M Jung,Glòria Martrus,Paul Kretschmer,Adrian F Sagebiel,Renée R C E Schreurs,Sven H Hagen,Gunter Burmester,Till S Clauditz,Steven T Pals,Michael Boettcher,Nathaniel Melling,Guido Sauter,Christian Tomuschat,Ingo Königs,Udo Schumacher,Marcus Altfeld,Jochem H Bernink,Daniel Perez,Konard Reinshagen
Early life is characterized by extraordinary challenges, including rapid tissue growth and immune adaptation to foreign antigens after birth. During this developmental stage, infants have an increased risk of immune-mediated diseases. Here, we demonstrate that tissue-resident, interleukin (IL)-13- and IL-4-producing group 2 innate lymphoid cells (ILC2s) are enriched in human infant intestines compared
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Nonoptimal bacteria species induce neutrophil-driven inflammation and barrier disruption in the female genital tract. Mucosal Immunol. (IF 8.0) Pub Date : 2023-04-29 Marina Costa-Fujishima,Atta Yazdanpanah,Samantha Horne,Alana Lamont,Paul Lopez,Christina Farr Zuend,Kenzie Birse,Morgan Taverner,Riley Greenslade,Max Abou,Laura Noel-Romas,Bernard Abrenica,Oluwaseun Ajibola,Nnamdi Ikeogu,Ruey-Chyi Su,Lyle R McKinnon,Helen Pymar,Vanessa Poliquin,Alicia R Berard,Adam D Burgener,Thomas T Murooka
Neutrophil recruitment and activation within the female genital tract are often associated with tissue inflammation, loss of vaginal epithelial barrier integrity, and increased risk for sexually transmitted infections, such as HIV-1. However, the direct role of neutrophils on vaginal epithelial barrier function during genital inflammation in vivo remains unclear. Using complementary proteome and immunological
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A bifurcated role for c-Maf in Th2 and Tfh2 cells during helminth infection. Mucosal Immunol. (IF 8.0) Pub Date : 2023-04-22 Katherine Bao,Uryan Isik Can,Mindy M Miller,Ivy K Brown,Mark Dell'Aringa,Hans Dooms,Max A Seibold,James Scott-Browne,Richard Lee Reinhardt
Differences in transcriptomes, transcription factor usage, and function have identified T follicular helper 2 (Tfh2) cells and T helper 2 (Th2) cells as distinct clusters of differentiation 4+",(CD4) T-cell subsets in settings of type-2 inflammation. Although the transcriptional programs driving Th2 cell differentiation and cytokine production are well defined, dependence on these classical Th2 programs
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iNKT cell-neutrophil crosstalk promotes colorectal cancer pathogenesis. Mucosal Immunol. (IF 8.0) Pub Date : 2023-03-31 Georgia Lattanzi,Francesco Strati,Angélica Díaz-Basabe,Federica Perillo,Chiara Amoroso,Giulia Protti,Maria Rita Giuffrè,Luca Iachini,Alberto Baeri,Ludovica Baldari,Elisa Cassinotti,Michele Ghidini,Barbara Galassi,Gianluca Lopez,Daniele Noviello,Laura Porretti,Elena Trombetta,Eleonora Messuti,Luca Mazzarella,Giandomenica Iezzi,Francesco Nicassio,Francesca Granucci,Maurizio Vecchi,Flavio Caprioli,Federica
iNKT cells account for a relevant fraction of effector T-cells in the intestine and are considered an attractive platform for cancer immunotherapy. Although iNKT cells are cytotoxic lymphocytes, their functional role in colorectal cancer (CRC) is still controversial, limiting their therapeutic use. Thus, we examined the immune cell composition and iNKT cell phenotype of CRC lesions in patients (n =
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Novel neuroendocrine role of γ-aminobutyric acid and gastrin-releasing peptide in the host response to influenza infection. Mucosal Immunol. (IF 8.0) Pub Date : 2023-03-24 Kari Ann Shirey,Wendy Lai,Mary E Sunday,Frank Cuttitta,Jorge C G Blanco,Stefanie N Vogel
Gastrin-releasing peptide (GRP), an evolutionarily conserved neuropeptide, significantly contributes to influenza-induced lethality and inflammation in rodent models. Because GRP is produced by pulmonary neuroendocrine cells (PNECs) in response to γ-aminobutyric acid (GABA), we hypothesized that influenza infection promotes GABA release from PNECs that activate GABAB receptors on PNECs to secrete GRP
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Systemically inoculated adjuvants stimulate pDC-dependent IgA response in local site. Mucosal Immunol. (IF 8.0) Pub Date : 2023-03-18 Eita Sasaki,Hideki Asanuma,Haruka Momose,Keiko Furuhata,Takuo Mizukami,Takayuki Matsumura,Yoshimasa Takahashi,Isao Hamaguchi
The stimulation of local immunity by vaccination is desirable for controlling virus replication in the respiratory tract. However, the local immune stimulatory effects of adjuvanted vaccines administered through the non-mucosal route are poorly understood. Here, we clarify the mechanisms by which non-mucosal inoculation of adjuvants stimulates the plasmacytoid dendritic cell (pDC)-dependent immunoglobulin
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Helios+ and RORγt+ Treg populations are differentially regulated by MHCII, CD28, and ICOS to shape the intestinal Treg pool. Mucosal Immunol. (IF 8.0) Pub Date : 2023-03-18 Elisa Cruz-Morales,Andrew P Hart,Georgia M Fossett,Terri M Laufer
Foxp3+ regulatory T cells (Tregs) are essential for intestinal homeostasis. Tregs in the small intestine include Helios+ thymus-derived Tregs (tTregs) and RORγt+ Tregs that differentiate in the periphery after antigenic stimulation (pTregs). TCR and costimulatory signals sustain Tregs with effector phenotypes, including those in the intestine, but it is unknown if tTregs and pTregs have similar requirements