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

Jason Twohig, Ana Cardus Figueras, Robert Andrews, Florian Wiede, Benjamin Cossins, Alicia Derrac Soria, Myles Lewis, Michael Townsend, David Millrine, David Hill, Javier Uceda Fernandez, Xiao Liu, Barbara Szomolay, Christopher Pepper, Philip Taylor, Costantino Pitzalis, Tony Tiganis, Nigel Williams, Gareth Jones, Simon JonesJasmine Li

Research output: Contribution to journalArticle (Academic Journal)peer-review

12 Citations (Scopus)
90 Downloads (Pure)

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 activation via the T cell antigen receptor limits IL-6’s control of STAT1 in effector and memory populations. Here we found that phosphorylation of STAT1 in response to IL-6 was regulated by the tyrosine phosphatases PTPN2 and PTPN22 expressed in response to the activation of naïve CD4 + T cells. Transcriptomics and chromatin immunoprecipitation–sequencing (ChIP-seq) 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, tyrosine phosphatases induced by the activation of naïve T cells determine the way activated or memory CD4 + T cells sense and interpret cytokine signals.

Original languageEnglish
Pages (from-to)458-470
Number of pages13
JournalNature Immunology
Volume20
Issue number4
Early online date19 Mar 2019
DOIs
Publication statusPublished - 10 Apr 2019

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