STING is an intrinsic checkpoint inhibitor that restrains the T(H)17 cell pathogenic program

Author(s):Show less -

Alves Damasceno, Luis Eduardo ; Martelossi Cebinelli, Guilherme Cesar ; Fernandes, Mariane Font ; Nascimento, Daniele Carvalho ; Publio, Gabriel Azevedo ; Ramirez Vinolo, Marco Aurelio ; Oliveira, Sergio Costa ; Sparwasser, Tim ; Cunha, Thiago Mattar ; Cunha, Fernando Queiroz ; Alves-Filho, Jose Carlos

• Document type: Journal article
• Source: CELL REPORTS; v. 39, n. 8, p. 15-pg., 2022-05-24.

Abstract

External and intrinsic factors regulate the transcriptional profile of T helper 17 (T(H)17) 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 T(H)17 cell pathogenic program. We demonstrate that non-pathogenic T(H)17 cells express higher levels of STING than those activated under pathogenic conditions. Activation of STING induces interleukin-10 (IL-10) production in T(H)17 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 Roryt transcriptional activity. Our findings reveal a regulatory function of STING in the T(H)17 cell activation program, proposing it as a valuable target to limit T(H)17-cell-mediated inflammation. (AU)

• FAPESP's process: 19/15070-0 - Determination of molecular and cellular mechanisms associated with Sepsis outcome using single cell RNA sequencing
• Grantee: Guilherme Cesar Martelossi Cebinelli
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/04170-1 - The role of DDX41 on the differentiation and function of regulatory T lymphocytes
• Grantee: Gabriel Azevedo Públio
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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: 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