Department of Cell Biology, Faculty of Science, Charles University, Prague, Czech Republic.
Laboratory of Immunobiology, Institute of Molecular Genetics of the Czech Academy of Sciences , Prague, Czech Republic.
J Exp Med. 2024 Jan 1;221(1). doi: 10.1084/jem.20230194. Epub 2023 Oct 30.
Intestinal epithelial cells have the capacity to upregulate MHCII molecules in response to certain epithelial-adhesive microbes, such as segmented filamentous bacteria (SFB). However, the mechanism regulating MHCII expression as well as the impact of epithelial MHCII-mediated antigen presentation on T cell responses targeting those microbes remains elusive. Here, we identify the cellular network that regulates MHCII expression on the intestinal epithelium in response to SFB. Since MHCII on the intestinal epithelium is dispensable for SFB-induced Th17 response, we explored other CD4+ T cell-based responses induced by SFB. We found that SFB drive the conversion of cognate CD4+ T cells to granzyme+ CD8α+ intraepithelial lymphocytes. These cells accumulate in small intestinal intraepithelial space in response to SFB. Yet, their accumulation is abrogated by the ablation of MHCII on the intestinal epithelium. Finally, we show that this mechanism is indispensable for the SFB-driven increase in the turnover of epithelial cells in the ileum. This study identifies a previously uncharacterized immune response to SFB, which is dependent on the epithelial MHCII function.
肠上皮细胞具有在响应某些上皮黏附微生物（如分段丝状菌[SFB]）时上调 MHCII 分子的能力。然而，调节 MHCII 表达的机制以及上皮 MHCII 介导的抗原呈递对针对这些微生物的 T 细胞反应的影响仍然难以捉摸。在这里，我们确定了调节肠上皮细胞对 SFB 反应中 MHCII 表达的细胞网络。由于肠上皮细胞上的 MHCII 对于 SFB 诱导的 Th17 反应不是必需的，因此我们探索了 SFB 诱导的其他基于 CD4+ T 细胞的反应。我们发现 SFB 驱动同源 CD4+ T 细胞向颗粒酶+ CD8α+上皮内淋巴细胞的转化。这些细胞在响应 SFB 时在小肠上皮内空间中积累。然而，它们的积累被肠上皮细胞 MHCII 的消融所阻断。最后，我们表明，这种机制对于 SFB 驱动的回肠上皮细胞周转率增加是必不可少的。这项研究确定了对 SFB 的一种以前未被表征的免疫反应，该反应依赖于上皮 MHCII 功能。
