| First Author | Damasceno LEA | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 8 | Pages | 110838 |
| PubMed ID | 35613599 | Mgi Jnum | J:328642 |
| Mgi Id | MGI:7284025 | Doi | 10.1016/j.celrep.2022.110838 |
| Citation | Damasceno LEA, et al. (2022) STING is an intrinsic checkpoint inhibitor that restrains the TH17 cell pathogenic program. Cell Rep 39(8):110838 |
| abstractText | External and intrinsic factors regulate the transcriptional profile of T helper 17 (TH17) 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 TH17 cell pathogenic program. We demonstrate that non-pathogenic TH17 cells express higher levels of STING than those activated under pathogenic conditions. Activation of STING induces interleukin-10 (IL-10) production in TH17 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 Rorgammat transcriptional activity. Our findings reveal a regulatory function of STING in the TH17 cell activation program, proposing it as a valuable target to limit TH17-cell-mediated inflammation. |
