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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, Li, Jasmine, Hill, David G., Uceda Fernandez, Javier, Liu, Xiao, Szomolay, Barbara, Pepper, Christopher J., Taylor, Philip R., Pitzalis, Costantino, Tiganis, Tony, Williams, Nigel M., Jones, Gareth W. and Jones, Simon A. 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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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)
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: 14 May 2022 20:11

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