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Inhibition of IL-2 responsiveness by IL-6 is required for the generation of GC-T cells. | LitMetric

AI Article Synopsis

Article Abstract

Sustained T cell receptor (TCR) stimulation is required for maintaining germinal center T follicular helper (GC-T) cells. Paradoxically, TCR activation induces interleukin-2 receptor (IL-2R) expression and IL-2 production, thereby initiating a feedback loop of IL-2 signaling that normally inhibits T cells. It is unclear how GC-T cells can receive prolonged TCR signaling without succumbing to the detrimental effects of IL-2. Using an influenza infection model, we show here that GC-T cells secreted large amounts of IL-2 but responded poorly to it. To maintain their IL-2 hyporesponsiveness, GC-T cells required intrinsic IL-6 signaling. Mechanistically, we found that IL-6 inhibited up-regulation of IL-2Rβ (CD122) by preventing association of STAT5 with the locus, thus allowing GC-T cells to receive sustained TCR signaling and produce IL-2 without initiating a TCR/IL-2 inhibitory feedback loop. Collectively, our results identify a regulatory mechanism that controls the generation of GC-T cells.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820141PMC
http://dx.doi.org/10.1126/sciimmunol.aaw7636DOI Listing

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