A clinically-relevant STING agonist restrains human TH17 cell inflammatory profile

Luis Eduardo Alves Damasceno; Thiago Mattar Cunha; Fernando Queiroz Cunha; Tim Sparwasser; José Carlos Alves-Filho

doi:10.1016/j.intimp.2023.111007

A clinically-relevant STING agonist restrains human T_H17 cell inflammatory profile

Int Immunopharmacol. 2023 Nov;124(Pt B):111007. doi: 10.1016/j.intimp.2023.111007. Epub 2023 Sep 29.

Authors

Luis Eduardo Alves Damasceno¹, Thiago Mattar Cunha², Fernando Queiroz Cunha², Tim Sparwasser³, José Carlos Alves-Filho⁴

Affiliations

¹ Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP 14049-900, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP 14049-900, Brazil; Institute of Medical Microbiology and Hygiene, University Medical Center of the Johannes Gutenberg-University, Mainz 55131, Germany.
² Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP 14049-900, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP 14049-900, Brazil.
³ Institute of Medical Microbiology and Hygiene, University Medical Center of the Johannes Gutenberg-University, Mainz 55131, Germany.
⁴ Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP 14049-900, Brazil; Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP 14049-900, Brazil. Electronic address: jcafilho@usp.br.

PMID: 37778170
DOI: 10.1016/j.intimp.2023.111007

Abstract

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 T_H17 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 T_H17 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 T_H17 cells. Of particular interest, 2'3'-c-di-AM(PS)₂(Rp,Rp) reduces IL-17A production and IL23R expression by human T_H17 cells while it favors the generation of regulatory T (T_reg) cells. These findings suggest that STING agonists may be promising approaches for treating human T_H17-mediated chronic inflammation.

Keywords: 2′3′-c-di-AM(PS)(2)(Rp,Rp); ADU-S100; Human T(H)17 cells; Rorγt; STING.

MeSH terms

Animals
Colitis* / pathology
Disease Models, Animal
Humans
Inflammation* / metabolism
Mice
Signal Transduction
Th17 Cells