MHC class II antigen presentation by intestinal epithelial cells fine-tunes bacteria-reactive CD4 T-cell responses.

Autor:	Heuberger CE; Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Janney A; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Ilott N; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Bertocchi A; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Pott S; Department of Human Genetics, University of Chicago, Chicago, United States., Gu Y; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Pohin M; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Friedrich M; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Mann EH; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Pearson C; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Powrie FM; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Pott J; Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Thornton E; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom., Maloy KJ; School of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom. Electronic address: Kevin.maloy@glasgow.ac.uk.
Jazyk:	angličtina
Zdroj:	Mucosal immunology [Mucosal Immunol] 2024 Jun; Vol. 17 (3), pp. 416-430. Date of Electronic Publication: 2023 May 19.
DOI:	10.1016/j.mucimm.2023.05.001
Abstrakt:	Although intestinal epithelial cells (IECs) can express major histocompatibility complex class II (MHC II), especially during intestinal inflammation, it remains unclear if antigen presentation by IECs favors pro- or anti-inflammatory CD4 + T-cell responses. Using selective gene ablation of MHC II in IECs and IEC organoid cultures, we assessed the impact of MHC II expression by IECs on CD4 + T-cell responses and disease outcomes in response to enteric bacterial pathogens. We found that intestinal bacterial infections elicit inflammatory cues that greatly increase expression of MHC II processing and presentation molecules in colonic IECs. Whilst IEC MHC II expression had little impact on disease severity following Citrobacter rodentium or Helicobacter hepaticus infection, using a colonic IEC organoid-CD4 + T cell co-culture system, we demonstrate that IECs can activate antigen-specific CD4 + T cells in an MHC II-dependent manner, modulating both regulatory and effector Th cell subsets. Furthermore, we assessed adoptively transferred H. hepaticus-specific CD4 + T cells during intestinal inflammation in vivo and report that IEC MHC II expression dampens pro-inflammatory effector Th cells. Our findings indicate that IECs can function as non-conventional antigen-presenting cells and that IEC MHC II expression fine-tunes local effector CD4 + T-cell responses during intestinal inflammation. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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