Why do intestinal epithelial cells express MHC class II?

Heuberger, C., Pott, J. and Maloy, K. J. (2021) Why do intestinal epithelial cells express MHC class II? Immunology, 162(4), pp. 357-367. (doi: 10.1111/imm.13270) (PMID:32966619) (PMCID:PMC7968399)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Maloy, Professor Kevin
Authors: Heuberger, C., Pott, J., and Maloy, K. J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Immunology
ISSN (Online):1365-2567
Published Online:23 September 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Immunology 162(4): 357-367
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
313264Regulation of intestinal immune homeostasis by NOD-like receptorsKevin MaloyWellcome Trust (WELLCOTR)102972/A/13/ZIII - Immunology