STING is an intrinsic checkpoint inhibitor that restrains the T H 17 cell pathogenic program.

External and intrinsic factors regulate the transcriptional profile of T helper 17 (T _H 17) cells, thereby affecting their pathogenic potential and revealing their context-dependent plasticity. The stimulator of interferon genes (STING), a component of the intracellular DNA-sensing pathway, triggers immune responses but remains largely unexplored in T cells. Here, we describe an intrinsic role of STING in limiting the T _H 17 cell pathogenic program. We demonstrate that non-pathogenic T _H 17 cells express higher levels of STING than those activated under pathogenic conditions. Activation of STING induces interleukin-10 (IL-10) production in T _H 17 cells, decreasing IL-17A and IL-23R expression in a type I interferon (IFN)-independent manner. Mechanistically, STING-induced IL-10 production partially requires aryl hydrocarbon receptor (AhR) signaling, while the decrease of IL-17A expression occurs due to a reduction of Rorγt transcriptional activity. Our findings reveal a regulatory function of STING in the T _H 17 cell activation program, proposing it as a valuable target to limit T _H 17-cell-mediated inflammation.
Competing Interests: Declaration of interests All authors declare no competing interests.
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