STING is an intrinsic checkpoint inhibitor that restrains the TH17 cell pathogenic program.

Cell reports 2022 May 24

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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 Rorγt 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. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Luis Eduardo Alves Damasceno, Guilherme Cesar Martelossi Cebinelli, Mariane Font Fernandes, Daniele Carvalho Nascimento, Gabriel Azevedo Públio, Marco Aurélio Ramirez Vinolo, Sergio Costa Oliveira, Tim Sparwasser, Thiago Mattar Cunha, Fernando Queiroz Cunha, José Carlos Alves-Filho. STING is an intrinsic checkpoint inhibitor that restrains the TH17 cell pathogenic program. Cell reports. 2022 May 24;39(8):110838