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)

Abstract

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
• Status: Published
• Refereed: Yes
• 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
• Publisher: Wiley
• ISSN: 0019-2805
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
313264		Regulation of intestinal immune homeostasis by NOD-like receptors	Kevin Maloy	Wellcome Trust (WELLCOTR)	102972/A/13/Z	III - Immunology