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

Author(s)

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

• Document type: Journal article
• Source: International Immunopharmacology; v. 124, p. 6-pg., 2023-09-29.

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(H)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 T(H)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 T(H)17 cells. Of particular interest, 2'3'-c-di-AM(PS)(2)(Rp,Rp) reduces IL-17A production and IL23R expression by human T(H)17 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(H)17-mediated chronic inflammation. (AU)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/17542-4 - The role of the STING signaling pathway in the regulation of Th17 cell pathogenicity and its implication for autoimmunity
• Grantee: Luis Eduardo Alves Damasceno
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 22/08412-5 - Understanding the molecular regulation of Th17 and regulatory T cells in infections and autoimmune diseases
• Grantee: José Carlos Farias Alves Filho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/08800-2 - Uncovering molecular mechanisms involved in STING-mediated regulation of Th17 cell pathogenicity
• Grantee: Luis Eduardo Alves Damasceno
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate