A genetic screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation

Cytokine-mediated activation of host immunity is central to the control of pathogens. Interferon-gamma (IFNγ) is a key cytokine in protective immunity that induces major histocompatibility complex class II molecules (MHCII) to amplify CD4+ T cell activation and effector function. Despite its central...

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Autores principales:	Michael C Kiritsy, Laurisa M Ankley, Justin Trombley, Gabrielle P Huizinga, Audrey E Lord, Pontus Orning, Roland Elling, Katherine A Fitzgerald, Andrew J Olive
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	IFN-gamma MHCII expression CD4+ T cell activation macrophages Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/27cb52ae4b22483f922ca3e06412e9cd
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spelling	oai:doaj.org-article:27cb52ae4b22483f922ca3e06412e9cd2021-11-17T09:45:37ZA genetic screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation10.7554/eLife.651102050-084Xe65110https://doaj.org/article/27cb52ae4b22483f922ca3e06412e9cd2021-11-01T00:00:00Zhttps://elifesciences.org/articles/65110https://doaj.org/toc/2050-084XCytokine-mediated activation of host immunity is central to the control of pathogens. Interferon-gamma (IFNγ) is a key cytokine in protective immunity that induces major histocompatibility complex class II molecules (MHCII) to amplify CD4+ T cell activation and effector function. Despite its central role, the dynamic regulation of IFNγ-induced MHCII is not well understood. Using a genome-wide CRISPR-Cas9 screen in murine macrophages, we identified genes that control MHCII surface expression. Mechanistic studies uncovered two parallel pathways of IFNγ-mediated MHCII control that require the multifunctional glycogen synthase kinase three beta (GSK3β) or the mediator complex subunit 16 (MED16). Both pathways control distinct aspects of the IFNγ response and are necessary for IFNγ-mediated induction of the MHCII transactivator Ciita, MHCII expression, and CD4+ T cell activation. Our results define previously unappreciated regulation of MHCII expression that is required to control CD4+ T cell responses.Michael C KiritsyLaurisa M AnkleyJustin TrombleyGabrielle P HuizingaAudrey E LordPontus OrningRoland EllingKatherine A FitzgeraldAndrew J OliveeLife Sciences Publications LtdarticleIFN-gammaMHCII expressionCD4+ T cell activationmacrophagesMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	IFN-gamma MHCII expression CD4+ T cell activation macrophages Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	IFN-gamma MHCII expression CD4+ T cell activation macrophages Medicine R Science Q Biology (General) QH301-705.5 Michael C Kiritsy Laurisa M Ankley Justin Trombley Gabrielle P Huizinga Audrey E Lord Pontus Orning Roland Elling Katherine A Fitzgerald Andrew J Olive A genetic screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation
description	Cytokine-mediated activation of host immunity is central to the control of pathogens. Interferon-gamma (IFNγ) is a key cytokine in protective immunity that induces major histocompatibility complex class II molecules (MHCII) to amplify CD4+ T cell activation and effector function. Despite its central role, the dynamic regulation of IFNγ-induced MHCII is not well understood. Using a genome-wide CRISPR-Cas9 screen in murine macrophages, we identified genes that control MHCII surface expression. Mechanistic studies uncovered two parallel pathways of IFNγ-mediated MHCII control that require the multifunctional glycogen synthase kinase three beta (GSK3β) or the mediator complex subunit 16 (MED16). Both pathways control distinct aspects of the IFNγ response and are necessary for IFNγ-mediated induction of the MHCII transactivator Ciita, MHCII expression, and CD4+ T cell activation. Our results define previously unappreciated regulation of MHCII expression that is required to control CD4+ T cell responses.
format	article
author	Michael C Kiritsy Laurisa M Ankley Justin Trombley Gabrielle P Huizinga Audrey E Lord Pontus Orning Roland Elling Katherine A Fitzgerald Andrew J Olive
author_facet	Michael C Kiritsy Laurisa M Ankley Justin Trombley Gabrielle P Huizinga Audrey E Lord Pontus Orning Roland Elling Katherine A Fitzgerald Andrew J Olive
author_sort	Michael C Kiritsy
title	A genetic screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation
title_short	A genetic screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation
title_full	A genetic screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation
title_fullStr	A genetic screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation
title_full_unstemmed	A genetic screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation
title_sort	genetic screen in macrophages identifies new regulators of ifnγ-inducible mhcii that contribute to t cell activation
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/27cb52ae4b22483f922ca3e06412e9cd
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A genetic screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation

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