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The role of the STING signaling pathway in the regulation of Th17 cell pathogenicity and its implication for autoimmunity

Grant number: 18/17542-4
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2020
Effective date (End): March 31, 2023
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:José Carlos Farias Alves Filho
Grantee:Luis Eduardo Alves Damasceno
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID
Associated scholarship(s):21/08800-2 - Uncovering molecular mechanisms involved in STING-mediated regulation of Th17 cell pathogenicity, BE.EP.DR

Abstract

Nucleic acids are essential carriers of genetic information of living organisms, however, it is known that tissue damage and cell death may result in release of DNA fragments, which in turn may directly activate the immune response. In this context, the adaptor protein STING (STimulator of INterferon Genes) was reported to be an important intracellular sensor for foreign and self-cytoplasmic DNA that activates a range of transcriptional factors, including those involved in type I IFN production. Although STING is broadly described in innate immune cells, little is known about its role in lymphocytes. It is noticeable that Th17 cells mediate the development of different autoimmune disorders, nevertheless, the dynamics of their pathogenicity is still poorly understood. Unexpectedly, our preliminary results demonstrate that STING activation is able to reduce IL-17 expression and concomitantly, increasing IL-10 production by Th17 cells under optimal conditions of differentiation. Thus, this research project aims to evaluate the influence of the STING signaling pathway on generation and regulation of Th17 cell pathogenicity and its consequences for autoimmunity. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
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; et al. STING is an intrinsic checkpoint inhibitor that restrains the T(H)17 cell pathogenic program. CELL REPORTS, v. 39, n. 8, p. 15-pg., . (19/15070-0, 20/04170-1, 18/17542-4, 13/08216-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
DAMASCENO, Luis Eduardo Alves. The STING signaling pathway limits the pathogenic potential of TH17 cells. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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