Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells

Md Moniruzzaman; M Arifur Rahman; Ran Wang; Kuan Yau Wong; Alice C-H Chen; Alexandra Mueller; Steven Taylor; Alexa Harding; Thishan Illankoon; Percival Wiid; Haressh Sajiir; Veronika Schreiber; Lucy D Burr; Michael A McGuckin; Simon Phipps; Sumaira Z Hasnain

doi:10.1084/jem.20230106

Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells

J Exp Med. 2023 Nov 6;220(11):e20230106. doi: 10.1084/jem.20230106. Epub 2023 Sep 11.

Authors

Md Moniruzzaman^#^{1

2}, M Arifur Rahman^#^{1

2}, Ran Wang^#^{1

2}, Kuan Yau Wong^{1

2}, Alice C-H Chen^{1

2}, Alexandra Mueller^{1

2}, Steven Taylor³, Alexa Harding², Thishan Illankoon^{1

2}, Percival Wiid^{1

2}, Haressh Sajiir^{1

2}, Veronika Schreiber², Lucy D Burr^{1

2

4}, Michael A McGuckin⁵, Simon Phipps^{1

6

7}, Sumaira Z Hasnain^{1

2

6}

Affiliations

¹ Faculty of Medicine, The University of Queensland , Brisbane, Australia.
² Immunopathology Group, Translational Research Institute, Mater Research Institute-The University of Queensland , Brisbane, Australia.
³ South Australian Health and Medical Research Institute , Adelaide, Australia.
⁴ Department of Respiratory and Sleep Medicine, Mater Health, South Brisbane, Australia.
⁵ Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne , Parkville, Australia.
⁶ Australian Infectious Diseases Research Centre, The University of Queensland , Brisbane, Australia.
⁷ Respiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Herston, Australia.

^# Contributed equally.

Abstract

Major histocompatibility complex (MHC) II is dynamically expressed on mucosal epithelial cells and is induced in response to inflammation and parasitic infections, upon exposure to microbiota, and is increased in chronic inflammatory diseases. However, the regulation of epithelial cell-specific MHC II during homeostasis is yet to be explored. We discovered a novel role for IL-22 in suppressing epithelial cell MHC II partially via the regulation of endoplasmic reticulum (ER) stress, using animals lacking the interleukin-22-receptor (IL-22RA1), primary human and murine intestinal and respiratory organoids, and murine models of respiratory virus infection or with intestinal epithelial cell defects. IL-22 directly downregulated interferon-γ-induced MHC II on primary epithelial cells by modulating the expression of MHC II antigen A α (H2-Aα) and Class II transactivator (Ciita), a master regulator of MHC II gene expression. IL-22RA1-knockouts have significantly higher MHC II expression on mucosal epithelial cells. Thus, while IL-22-based therapeutics improve pathology in chronic disease, their use may increase susceptibility to viral infections.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Endoplasmic Reticulum Stress
Epithelial Cells
Humans
Interleukin-22
Interleukins*
Major Histocompatibility Complex*
Mice

Substances

Interleukins