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

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 J. Pepper, Philip R. Taylor, Costantino Pitzalis, Tony Tiganis, Nigel M. Williams, Gareth W. Jones & 1 others Simon A. Jones

Research output: Contribution to journalArticleResearchpeer-review

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
DOIs
Publication statusPublished - 1 Apr 2019

Cite this

Twohig, J. P., Cardus Figueras, A., Andrews, R., Wiede, F., Cossins, B. C., Derrac Soria, A., ... Jones, S. 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(4), 458-470. https://doi.org/10.1038/s41590-019-0350-0
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. ; Jones, Simon A. / Activation of naïve CD4 + T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4 + T cells. In: Nature Immunology. 2019 ; Vol. 20, No. 4. pp. 458-470.
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title = "Activation of na{\"i}ve CD4 + T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4 + T cells",
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 na{\"i}ve CD4 + T cells. Transcriptomics and chromatin immunoprecipitation–sequencing (ChIP-seq) of IL-6 responses in na{\"i}ve 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 na{\"i}ve T cells determine the way activated or memory CD4 + T cells sense and interpret cytokine signals.",
author = "Twohig, {Jason P.} and {Cardus Figueras}, Ana and Robert Andrews and Florian Wiede and Cossins, {Benjamin C.} and {Derrac Soria}, Alicia and Lewis, {Myles J.} and Townsend, {Michael J.} and David Millrine and Jasmine Li and Hill, {David G.} and {Uceda Fernandez}, Javier and Xiao Liu and Barbara Szomolay and Pepper, {Christopher J.} and Taylor, {Philip R.} and Costantino Pitzalis and Tony Tiganis and Williams, {Nigel M.} and Jones, {Gareth W.} and Jones, {Simon A.}",
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Twohig, JP, Cardus Figueras, A, Andrews, R, Wiede, F, Cossins, BC, Derrac Soria, A, Lewis, MJ, Townsend, MJ, Millrine, D, Li, J, Hill, DG, Uceda Fernandez, J, Liu, X, Szomolay, B, Pepper, CJ, Taylor, PR, Pitzalis, C, Tiganis, T, Williams, NM, Jones, GW & Jones, SA 2019, 'Activation of naïve CD4 + T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4 + T cells' Nature Immunology, vol. 20, no. 4, pp. 458-470. https://doi.org/10.1038/s41590-019-0350-0

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.; Jones, Simon A.

In: Nature Immunology, Vol. 20, No. 4, 01.04.2019, p. 458-470.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Activation of naïve CD4 + T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4 + T cells

AU - Twohig, Jason P.

AU - Cardus Figueras, Ana

AU - Andrews, Robert

AU - Wiede, Florian

AU - Cossins, Benjamin C.

AU - Derrac Soria, Alicia

AU - Lewis, Myles J.

AU - Townsend, Michael J.

AU - Millrine, David

AU - Li, Jasmine

AU - Hill, David G.

AU - Uceda Fernandez, Javier

AU - Liu, Xiao

AU - Szomolay, Barbara

AU - Pepper, Christopher J.

AU - Taylor, Philip R.

AU - Pitzalis, Costantino

AU - Tiganis, Tony

AU - Williams, Nigel M.

AU - Jones, Gareth W.

AU - Jones, Simon A.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

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JO - Nature Immunology

JF - Nature Immunology

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