Naïve T-cell activation 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, Jasmine Li, David Hill, Javier Uceda Fernandez, David Millrine, Xiao Liu, Barbara Szomolay, Christopher J. Pepper, Philip R. Taylor, Tony Tiganis, Nigel M. Williams, Gareth W. Jones Simon A. Jones*

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.



Here are the links to the interactive figures mentioned within the paper:
Differentially expressed genes upregulated in Naive or Tem with stimulation Figure 2E
Comparison of ChIP-seq peaks and Affymetrix differential expression Figure 6C
Common & Unique pathways identified in Naive & Tem comparison Supplemental Figure 6A