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Aryl Hydrocarbon Receptor Activity in Intestinal Epithelial Cells in the Formation of Colonic Tertiary Lymphoid Tissues
American Journal of Physiology-Gastrointestinal and Liver Physiology ( IF 4.5 ) Pub Date : 2024-04-02 , DOI: 10.1152/ajpgi.00274.2023
Erika Leonor Garcia-Villatoro 1 , Arinzechukwu Ufondu 2 , Evelyn S. Callaway 2 , Kimberly Allred 3 , Stephen H. Safe 4 , Robert S. Chapkin 5 , Arul Jayaraman 2 , Clinton D. Allred 3
Affiliation  

After birth, the development of secondary lymphoid tissues (SLTs) in the colon is dependent on the expression of the Aryl Hydrocarbon Receptor (AhR) in immune cells as a response to the availability of AhR ligands. However, little is known about how AhR activity from intestinal epithelial cells (IECs) may influence the development of tertiary lymphoid tissues (TLTs). As organized structures that develop at sites of inflammation or infection during adulthood, TLTs serve as localized centers of adaptive immune responses, and their presence has been associated with the resolution of inflammation and tumorigenesis in the colon. Here, we investigated the effect of the conditional loss of AhR activity in IECs in the formation and immune cell composition of TLTs in a model of acute inflammation. In females, loss of AhR activity in IECs reduced the formation of TLTs without significantly changing disease outcomes nor immune cell composition within TLTs. In males lacking AhR expression in IECs, increased disease activity index, lower expression of functional-IEC genes, increased number of TLTs, increased T-cell density, and lower B- to T-cell ratio was observed. These findings may represent an unfavorable prognosis when exposed to DSS-induced epithelial damage compared to females. Sex and loss of IEC AhR also resulted in changes in microbial populations in the gut. Collectively, these data suggest that the formation of TLTs in the colon is influenced by sex and AhR expression in IECs.

中文翻译:

结肠三级淋巴组织形成中肠上皮细胞芳基烃受体活性

出生后,结肠中次级淋巴组织 (SLT) 的发育依赖于免疫细胞中芳基烃受体 (AhR) 的表达,作为对 AhR 配体可用性的反应。然而,关于肠上皮细胞 (IEC) 的 AhR 活性如何影响三级淋巴组织 (TLT) 的发育,人们知之甚少。作为成年期炎症或感染部位形成的有组织结构,TLT 作为适应性免疫反应的局部中心,它们的存在与结肠炎症和肿瘤发生的消退有关。在这里,我们研究了急性炎症模型中 IEC 中 AhR 活性有条件丧失对 TLT 形成和免疫细胞组成的影响。在女性中,IEC 中 AhR 活性的丧失减少了 TLT 的形成,但没有显着改变疾病结果或 TLT 内的免疫细胞组成。在 IEC 中缺乏 AhR 表达的男性中,观察到疾病活动指数增加、功能性 IEC 基因表达降低、TLT 数量增加、T 细胞密度增加以及 B 细胞与 T 细胞比率降低。这些发现可能代表与女性相比,当暴露于 DSS 诱导的上皮损伤时,预后较差。性别和 IEC AhR 的丧失也导致肠道微生物种群的变化。总的来说,这些数据表明结肠中 TLT 的形成受到性别和 IEC 中 AhR 表达的影响。
更新日期:2024-04-02
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