Ptpn2 and KLRG1 regulate the generation and function of tissue-resident memory CD8 + T cells in skin

dc.contributor.authorHochheiser, Katherina
dc.contributor.authorWiede, Florian
dc.contributor.authorWagner, Teagan
dc.contributor.authorFreestone, David
dc.contributor.authorEnders, Matthias H
dc.contributor.authorOlshansky, Moshe
dc.contributor.authorRuss, Brendan
dc.contributor.authorNüssing, Simone
dc.contributor.authorBawden, Emma
dc.contributor.authorBraun, Asolina
dc.contributor.authorTscharke, David
dc.date.accessioned2022-10-31T04:29:19Z
dc.date.available2022-10-31T04:29:19Z
dc.date.issued2021
dc.date.updated2021-11-28T07:25:42Z
dc.description.abstractTissue-resident memory T cells (T cells) are key elements of tissue immunity. Here, we investigated the role of the regulator of T cell receptor and cytokine signaling, Ptpn2, in the formation and function of T cells in skin. Ptpn2-deficient CD8 T cells displayed a marked defect in generating CD69 CD103 T cells in response to herpes simplex virus type 1 (HSV-1) skin infection. This was accompanied by a reduction in the proportion of KLRG1 memory precursor cells and a transcriptional bias toward terminal differentiation. Of note, forced expression of KLRG1 was sufficient to impede T cell formation. Normalizing memory precursor frequencies by transferring equal numbers of KLRG1− cells restored T generation, demonstrating that Ptpn2 impacted skin seeding with precursors rather than downstream T cell differentiation. Importantly, Ptpn2-deficient T cells augmented skin autoimmunity but also afforded superior protection from HSV-1 infection. Our results emphasize that KLRG1 repression is required for optimal T cell formation in skin and reveal an important role of Ptpn2 in regulating TRM cell functionality.en_AU
dc.description.sponsorshipK. Hochheiser was supported by the German Research Council (grant HO 5417/1-1) and is a Rhian and Paul Brazis Fellow in Translational Melanoma Immunology administered by the Peter MacCallum Cancer Foundation. T. Gebhardt is a Senior Biomedical Research Fellow supported by the Sylvia and Charles Viertel Charitable Foundationen_AU
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn0022-1007en_AU
dc.identifier.urihttp://hdl.handle.net/1885/276821
dc.language.isoen_AUen_AU
dc.provenanceThis article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/)en_AU
dc.publisherRockefeller University Pressen_AU
dc.relationhttp://purl.org/au-research/grants/nhmrc/1186575en_AU
dc.relationhttp://purl.org/au-research/grants/nhmrc/1156095en_AU
dc.relationhttp://purl.org/au-research/grants/nhmrc/1084805en_AU
dc.relationhttp://purl.org/au-research/grants/nhmrc/1184615en_AU
dc.rights© 2021 The authorsen_AU
dc.rights.licenseCreative Commons Attribution licenceen_AU
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/en_AU
dc.sourceJournal of Experimental Medicineen_AU
dc.titlePtpn2 and KLRG1 regulate the generation and function of tissue-resident memory CD8 + T cells in skinen_AU
dc.typeJournal articleen_AU
dcterms.accessRightsOpen Accessen_AU
local.bibliographicCitation.issue6en_AU
local.contributor.affiliationHochheiser, Katherina, Department of Microbiology and Immunologyen_AU
local.contributor.affiliationWiede, Florian, Monash Universityen_AU
local.contributor.affiliationWagner, Teagan, The University of Melbourne at the Peter Doherty Institute for Infection & Immunityen_AU
local.contributor.affiliationFreestone, David, The University of Melbourne at the Peter Doherty Institute for Infection & Immunityen_AU
local.contributor.affiliationEnders, Matthias H, University of Melbourneen_AU
local.contributor.affiliationOlshansky, Moshe, Monash Universityen_AU
local.contributor.affiliationRuss, Brendan, Monash Universityen_AU
local.contributor.affiliationNüssing, Simone, Peter MacCallum Cancer Centre Melbourneen_AU
local.contributor.affiliationBawden, Emma, The University of Melbourne at the Peter Doherty Institute for Infection & Immunityen_AU
local.contributor.affiliationBraun, Asolina, The University of Melbourne at the Peter Doherty Institute for Infection & Immunityen_AU
local.contributor.affiliationTscharke, David, College of Health and Medicine, ANUen_AU
local.contributor.authoremailu4334102@anu.edu.auen_AU
local.contributor.authoruidTscharke, David, u4334102en_AU
local.description.notesImported from ARIESen_AU
local.identifier.absfor320404 - Cellular immunologyen_AU
local.identifier.absseo280103 - Expanding knowledge in the biomedical and clinical sciencesen_AU
local.identifier.ariespublicationa383154xPUB19293en_AU
local.identifier.citationvolume218en_AU
local.identifier.doi10.1084/jem.20200940en_AU
local.identifier.scopusID2-s2.0-85104978015
local.identifier.uidSubmittedBya383154en_AU
local.publisher.urlhttps://rupress.org/en_AU
local.type.statusPublished Versionen_AU

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