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A clinically-relevant STING agonist restrains human T H 17 cell inflammatory profile.
International Immunopharmacology 2023 September 30
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 TH 17 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 TH 17 pro-inflammatory program in vitro. Here we demonstrate that 2'3'-c-di-AM(PS)2 (Rp,Rp), a STING agonist that has been undergoing clinical trials for antitumor immunotherapy, activates the STING signalosome in differentiating human TH 17 cells. Of particular interest, 2'3'-c-di-AM(PS)2 (Rp,Rp) reduces IL-17A production and IL23R expression by human TH 17 cells while it favors the generation of regulatory T (Treg ) cells. These findings suggest that STING agonists may be promising approaches for treating human TH 17-mediated chronic inflammation.
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