Nature Immunology-19.pdf (63.83 MB)
Activation of naïve CD4+ T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4+ T cells
journal contribution
posted on 2023-06-09, 17:20 authored by Jason P Twohig, Ana Cardus Figueras, Robert Andrews, Florian Wiede, Benjamin C Cossins, Alicia Derrac Soria, Myles J Lewis, Michael J Townsend, David Millrine, Jasmine Li, David G Hill, Javier Uceda Fernandez, Xiao Liu, Barbara Szomolay, Christopher PepperChristopher Pepper, Philip R Taylor, Costantino Pitzalis, Tony Tiganis, Nigel M Williams, Gareth W Jones, Simon A JonesThe 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.
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Publication status
- Published
File Version
- Accepted version
Journal
Nature ImmunologyISSN
1529-2908Publisher
Nature ResearchExternal DOI
Volume
20Page range
458-470Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2019-03-21First Open Access (FOA) Date
2019-09-19First Compliant Deposit (FCD) Date
2019-03-20Usage metrics
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