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Updated: Jul 12, 2025
Intravital Imaging of Intraepithelial Lymphocytes in Murine Small Intestine
Published on: June 24, 2019
Segmented filamentous bacteria-induced epithelial MHCII regulates cognate CD4+ IELs and epithelial turnover
Tomáš Brabec1,2, Martin Schwarzer3, Katarína Kováčová1
1Department of Cell Biology, Faculty of Science, Charles University, Prague, Czech Republic.
Abstract:
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.
Insights
Segmented filamentous bacteria (SFB) trigger a novel immune response in the gut. Epithelial cells use MHCII molecules to promote CD4+ T cells, which are crucial for intestinal epithelial cell turnover.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Intestinal epithelial cells can express MHCII molecules in response to microbes like SFB.
- The regulation and function of epithelial MHCII in response to SFB are not well understood.
Purpose of the Study:
- To elucidate the mechanism controlling MHCII expression on intestinal epithelial cells induced by SFB.
- To investigate the role of epithelial MHCII in T cell responses against SFB and subsequent host responses.
Main Methods:
- Investigated the cellular network regulating MHCII expression in response to SFB.
- Analyzed T cell responses, specifically CD4+ T cell conversion to granzyme+ CD8α+ intraepithelial lymphocytes.
- Utilized MHCII-deficient models to assess the impact of epithelial MHCII ablation.
Main Results:
- Identified a cellular network regulating SFB-induced MHCII expression on intestinal epithelial cells.
- Found that SFB induce CD4+ T cells to become granzyme+ CD8α+ intraepithelial lymphocytes.
- Demonstrated that epithelial MHCII is essential for the accumulation of these lymphocytes and for SFB-driven epithelial cell turnover in the ileum.
Conclusions:
- Discovered a previously unknown immune response to SFB mediated by epithelial MHCII.
- Epithelial MHCII is critical for generating a specific CD4+ T cell population (granzyme+ CD8α+ IELs) that drives intestinal epithelial cell turnover.
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