Why do intestinal epithelial cells express MHC class II?
Why do intestinal epithelial cells express MHC class II?
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DOI：
10.1111/imm.13270
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发表时间：
2021-04
期刊：
影响因子：
6.4
通讯作者：
Maloy KJ
中科院分区：
文献类型：
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作者：
Heuberger C;Pott J;Maloy KJ
肠上皮细胞（IEC）构成肠腔中存在的大量抗原负荷与粘膜免疫区室之间的边界。它们表达抗原加工和呈递机制的能力引起了IEC是否作为非常规抗原呈递细胞发挥作用的问题。非造血细胞（如IEC）的主要组织相容性复合物（MHC）II类表达受II类反式激活因子（CIITA）的严格调控，通常由IFN-γ诱导。由于IEC的MHC II类表达在炎症条件下上调，因此已经提出激活效应CD 4 + T（Teff）细胞。然而，其他研究报告了相互矛盾的结果，而是通过调节性T（Treg）细胞活化，提出了IEC的抗原呈递抑制作用。最近研究IEC释放的MHC II类+外泌体的作用的研究也报告了免疫增强或免疫抑制活性的相互矛盾的发现。此外，除了调节炎症反应，最近的研究结果表明，MHC II类表达的肠干细胞可能会引起串扰，促进上皮更新。IEC MHC II类抗原呈递的不同后果的更完整的理解将指导未来的努力，以调节这一途径选择性地调用保护性免疫，同时保持耐受性有益抗原。肠上皮细胞（IEC）可以在稳态和炎症过程中表达MHC II类分子，这表明它们可以塑造局部CD 4 + T细胞对肠道抗原的反应。然而，IEC对MHC II类抗原呈递的结果似乎依赖于环境，导致促炎反应增强或致耐受性调节性T细胞活化。更好地了解IEC表达MHC II类分子的功能可能有助于设计新的肠道疾病治疗方法，从而增强保护性免疫或改善有害的炎症。
Intestinal epithelial cells (IECs) constitute the border between the vast antigen load present in the intestinal lumen and the mucosal immune compartment. Their ability to express antigen processing and presentation machinery evokes the question whether IECs function as non‐conventional antigen‐presenting cells. Major histocompatibility complex (MHC) class II expression by non‐haematopoietic cells, such as IECs, is tightly regulated by the class II transactivator (CIITA) and is classically induced by IFN‐γ. As MHC class II expression by IECs is upregulated under inflammatory conditions, it has been proposed to activate effector CD4+ T (Teff) cells. However, other studies have reported contradictory results and instead suggested a suppressive role of antigen presentation by IECs, through regulatory T (Treg)‐cell activation. Recent studies investigating the role of MHC class II + exosomes released by IECs also reported conflicting findings of either immune enhancing or immunosuppressive activities. Moreover, in addition to modulating inflammatory responses, recent findings suggest that MHC class II expression by intestinal stem cells may elicit crosstalk that promotes epithelial renewal. A more complete understanding of the different consequences of IEC MHC class II antigen presentation will guide future efforts to modulate this pathway to selectively invoke protective immunity while maintaining tolerance to beneficial antigens. Intestinal epithelial cells (IECs) can express MHC class II molecules both at steady state and during inflammation, suggesting that they may shape local CD4+ T‐cell responses towards intestinal antigens. However, the outcome of MHC class II antigen presentation by IECs appears context dependent, resulting in either enhanced pro‐inflammatory responses or in tolerogenic regulatory T‐cell activation. A better understanding of the functions of MHC class II expression by IECs may allow the design of new therapies for intestinal diseases, which either enhance protective immunity or ameliorate harmful inflammation.
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DOI：
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