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Activation of naïve CD4+ T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4+ T cells

Twohig, Jason P., Cardus Figueras, Ana, Andrews, Robert, Wiede, Florian, Cossins, Benjamin C., Derrac Soria, Alicia, Lewis, Myles J., Townsend, Michael J., Millrine, David ORCID: https://orcid.org/0000-0002-8041-0151, Li, Jasmine, Hill, David G., Uceda Fernandez, Javier, Liu, Xiao, Szomolay, Barbara ORCID: https://orcid.org/0000-0002-5375-5533, Pepper, Christopher J., Taylor, Philip R. ORCID: https://orcid.org/0000-0003-0163-1421, Pitzalis, Costantino, Tiganis, Tony, Williams, Nigel M. ORCID: https://orcid.org/0000-0003-1177-6931, Jones, Gareth W. and Jones, Simon A. ORCID: https://orcid.org/0000-0001-7297-9711 2019. Activation of naïve CD4+ T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4+ T cells. Nature Immunology 20 , pp. 458-470. 10.1038/s41590-019-0350-0

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Abstract

The cytokine IL-6 controls the survival, proliferation and effector characteristics of lymphocytes through activation of the transcription factors STAT1 and STAT3. While STAT3 activity is an ever-present feature of IL-6 signaling in CD4+ T cells, prior T-cell receptor activation limits the IL-6 control of STAT1 in effector and memory populations. Here we show that STAT1 phosphorylation in response to IL-6 was regulated by protein tyrosine phosphatases (PTPN2, PTPN22) expressed in response to the activation of naïve CD4+T cells. Transcriptomic and chromatin immunoprecipitation-sequencing of IL-6 responses in naïve and effector memory CD4+ T cells showed how the suppression of STAT1 activation shaped the functional identity and effector characteristics of memory CD4+ T cells. Thus, protein tyrosine phosphatases induced by activation of naïve T cells determined the way activated or memory CD4+ T cells sensed and interpreted cytokine signals.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Advanced Research Computing @ Cardiff (ARCCA)
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RB Pathology
R Medicine > RM Therapeutics. Pharmacology
Publisher: Nature Publishing Group
ISSN: 1529-2908
Funders: Versus Arthritis, The Wellcome Trust, Medical Research Council, Roche, British Council, National Health and Medical Research council of Australia, Kidney Research UK
Date of First Compliant Deposit: 18 February 2019
Date of Acceptance: 14 February 2019
Last Modified: 30 May 2024 18:15
URI: https://orca.cardiff.ac.uk/id/eprint/119564

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