A clinically-relevant STING agonist restrains human T17 cell inflammatory profile.

The STING signaling pathway has gained attention over the last few years due to its ability to incite antimicrobial and antitumoral immunity. Conversely, in mouse models of autoimmunity such as colitis and multiple sclerosis, where T17 cells are implicated in tissue inflammation, STING activation has been associated with the attenuation of immunogenic responses. In this line, STING was found to limit murine T17 pro-inflammatory program in vitro. Here we demonstrate that 2'3'-c-di-AM(PS)(Rp,Rp), a STING agonist that has been undergoing clinical trials for antitumor immunotherapy, activates the STING signalosome in differentiating human T17 cells. Of particular interest, 2'3'-c-di-AM(PS)(Rp,Rp) reduces IL-17A production and IL23R expression by human T17 cells while it favors the generation of regulatory T (T) cells. These findings suggest that STING agonists may be promising approaches for treating human T17-mediated chronic inflammation.