The role of the p53 and STING signaling pathways integration in the modulation of the Th17 lymphocytes differentiation

• Grant number: 23/14926-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: Gabriel Alberto de Carvalho Barbosa
• 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

Abstract

p53 is a transcription factor necessary for maintaining the integrity of the genome, and theactivation of its pathway is triggered through signals of cellular stress and genomic instability, which act on specific mechanisms that define the cell's fate, such as blocking the cell cycle, senescence, DNA repair and apoptosis. In turn, the STING protein (STimulator of INterferonGenes) plays an important role in the detection of DNA and nucleic acids of microbial or endogenous origin, promoting the activation of a variety of transcription factors, including those involved in regulating the immune response. Although p53 is extensively described in cancer biology, little is known about its interaction with the STING pathway, as well as the regulation of the immune response. Our preliminary results demonstrate that p53 activation initiates IL-17A expression, while increasing FoxP3 expression in cultured lymphocytes under conditions of differentiation towards the Th17 phenotype, with activation of the STING pathway producing similar effects. Thus, the present project proposes to evaluate the importance of the p53 and STING signaling pathways integration in modulation of the Th17 lymphocytes differentiation and the development of autoimmune diseases.