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

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...

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Autores principales: Moniruzzaman, Md, Rahman, M. Arifur, Wang, Ran, Wong, Kuan Yau, Chen, Alice C.-H., Mueller, Alexandra, Taylor, Steven, Harding, Alexa, Illankoon, Thishan, Wiid, Percival, Sajiir, Haressh, Schreiber, Veronika, Burr, Lucy D., McGuckin, Michael A., Phipps, Simon, Hasnain, Sumaira Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494524/
https://www.ncbi.nlm.nih.gov/pubmed/37695525
http://dx.doi.org/10.1084/jem.20230106
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author Moniruzzaman, Md
Rahman, M. Arifur
Wang, Ran
Wong, Kuan Yau
Chen, Alice C.-H.
Mueller, Alexandra
Taylor, Steven
Harding, Alexa
Illankoon, Thishan
Wiid, Percival
Sajiir, Haressh
Schreiber, Veronika
Burr, Lucy D.
McGuckin, Michael A.
Phipps, Simon
Hasnain, Sumaira Z.
author_facet Moniruzzaman, Md
Rahman, M. Arifur
Wang, Ran
Wong, Kuan Yau
Chen, Alice C.-H.
Mueller, Alexandra
Taylor, Steven
Harding, Alexa
Illankoon, Thishan
Wiid, Percival
Sajiir, Haressh
Schreiber, Veronika
Burr, Lucy D.
McGuckin, Michael A.
Phipps, Simon
Hasnain, Sumaira Z.
author_sort Moniruzzaman, Md
collection PubMed
description 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.
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spelling pubmed-104945242023-09-12 Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells Moniruzzaman, Md Rahman, M. Arifur Wang, Ran Wong, Kuan Yau Chen, Alice C.-H. Mueller, Alexandra Taylor, Steven Harding, Alexa Illankoon, Thishan Wiid, Percival Sajiir, Haressh Schreiber, Veronika Burr, Lucy D. McGuckin, Michael A. Phipps, Simon Hasnain, Sumaira Z. J Exp Med Brief Definitive Report 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. Rockefeller University Press 2023-09-11 /pmc/articles/PMC10494524/ /pubmed/37695525 http://dx.doi.org/10.1084/jem.20230106 Text en © 2023 Moniruzzaman et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Definitive Report
Moniruzzaman, Md
Rahman, M. Arifur
Wang, Ran
Wong, Kuan Yau
Chen, Alice C.-H.
Mueller, Alexandra
Taylor, Steven
Harding, Alexa
Illankoon, Thishan
Wiid, Percival
Sajiir, Haressh
Schreiber, Veronika
Burr, Lucy D.
McGuckin, Michael A.
Phipps, Simon
Hasnain, Sumaira Z.
Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells
title Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells
title_full Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells
title_fullStr Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells
title_full_unstemmed Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells
title_short Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells
title_sort interleukin-22 suppresses major histocompatibility complex ii in mucosal epithelial cells
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494524/
https://www.ncbi.nlm.nih.gov/pubmed/37695525
http://dx.doi.org/10.1084/jem.20230106
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