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Germinal Center-Related G Protein-Coupled Receptors in Antibody-Mediated Autoimmune Skin Diseases: from Basic Research to Clinical Trials

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Abstract

Germinal center (GC) reaction greatly contributes to the humoral immune response, which begins in lymph nodes or other secondary lymphoid organs after follicular B cells are activated by T-dependent antigens. The GCs then serve as a platform for follicular B cells to complete clonal expansion and somatic hypermutation and then interact with follicular dendritic cells (FDC) and follicular helper T cells (Tfh). Through the interaction between the immune cells, significant processes of the humoral immune response are accomplished, such as antibody affinity maturation, class switching, and production of memory B cells and plasma cells. Cell positioning during the GC reaction is mainly mediated by the chemokine receptors and lipid receptors, which both belong to G protein-coupled receptors (GPCRs) family. There are some orphan GPCRs whose endogenous ligands are unclear yet contribute to the regulation of GC reaction as well. This review will give an introduction on the ligands and functions of two types of GC-relating GPCRs—chemokine receptors like CXCR4 and CXCR5, as well as emerging de-orphanized GPCRs like GPR183, GPR174, and P2RY8. The roles these GPCRs play in several antibody-mediated autoimmune skin diseases will be also discussed, including systemic lupus erythematosus (SLE), pemphigus, scleroderma, and dermatomyositis. Besides, GPCRs are excellent drug targets due to the unique structure and vital functions. Therefore, this review is aimed at providing readers with a focused knowledge about the role that GPCRs play in GC reaction, as well as in provoking the development of GPCR-targeting agents for immune-mediated diseases besides autoimmune diseases.

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Funding

This work was supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2020-RC320-003], the National Natural Science Foundation of China [Nos. 81972943, 81830097], Hunan Talent Young Investigator [No. 2019RS2012], Hunan Outstanding Young Investigator [No. 2020JJ2055], CAMS Innovation Fund for Medical Sciences (CIFMS) [2019-I2M-5–033], and Chongqing International Institute for Immunology [2020YJC10].

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Authors and Affiliations

  1. Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China

    Pengpeng Cao, Ming Yang & Haijing Wu

  2. Division of Pediatric Immunology and Allergy, Joe DiMaggio Children’s Hospital, Hollywood, FL, 33021, USA

    Christopher Chang

  3. Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, Davis, CA, 95616, USA

    Christopher Chang

  4. Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, 12 Jiangwangmiao Street, Nanjing, 210042, China

    Qianjin Lu

  5. Key Laboratory of Basic and Translational Research On Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China

    Qianjin Lu

  6. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China

    Qianjin Lu

  7. Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital, Central South University, Changsha, China

    Qianjin Lu

Authors
  1. Pengpeng Cao
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  2. Ming Yang
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  3. Christopher Chang
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  4. Haijing Wu
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  5. Qianjin Lu
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Contributions

PP C wrote the manuscript; M Y did the editing; C C, HJ W, and QJ L revised the manuscript.

Corresponding authors

Correspondence to Haijing Wu or Qianjin Lu.

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Cao, P., Yang, M., Chang, C. et al. Germinal Center-Related G Protein-Coupled Receptors in Antibody-Mediated Autoimmune Skin Diseases: from Basic Research to Clinical Trials. Clinic Rev Allerg Immunol 63, 357–370 (2022). https://doi.org/10.1007/s12016-022-08936-y

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