Activation of naïve CD4+ T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4+ T cells
| Autor: | Simon Arnett Jones, Jasmine Li, Florian Wiede, Michael J. Townsend, Gareth W. Jones, Xiao Liu, Costantino Pitzalis, Robert Andrews, Jason Peter Twohig, Alicia Derrac Soria, Philip R. Taylor, Javier Uceda Fernandez, Tony Tiganis, Barbara Szomolay, David Hill, Myles Lewis, Chris Pepper, Benjamin C. Cossins, Nigel Williams, Ana Cardus Figueras, David Millrine |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
RM Effector Chemistry medicine.medical_treatment Immunology Protein tyrosine phosphatase Chromatin Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Cytokine Antigen QR180 medicine Immunology and Allergy Phosphorylation Signal transduction Tyrosine RB 030215 immunology |
| Zdroj: | Twohig, J, Figueras, A C, Andrews, R, Wiede, F, Cossins, B, Soria, A D, Lewis, M, Townsend, M, Millrine, D, Hill, D, Fernandez, J U, Liu, X, Szomolay, B, Pepper, C, Taylor, P, Pitzalis, C, Tiganis, T, Williams, N, Jones, G, Jones, S & Li, J 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 |
| ISSN: | 1529-2916 1529-2908 |
| DOI: | 10.1038/s41590-019-0350-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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