STAT4 regulation of Th17 pathogenicity

/Abstract Autoimmune and chronic inflammatory diseases are on the rise in the United States and world-wide. The etiology of most autoimmune and chronic inflammatory diseases is not known; however it is proposed that a combination of genetic and environmental factors influence disease susceptibility. Genome wide association studies of multiple autoimmune and chronic inflammatory disorders have identified single nucleotide polymorphisms in several immunologically relevant genes that are linked to disease susceptibility, including the members of the IL-23/Th17 family and the human STAT4 gene. How STAT4 is coupled to the etiology of autoimmune and chronic inflammation is not known, therefore it is imperative to understand the function of STAT4 in the context of disease. The overarching hypothesis that STAT4 is a master regulator to IL-23 mediated chronic inflammatory and/or autoimmune disease by promoting the differentiation of pathogenic Th17 cells and coordinately suppressing the emergence of anti-inflammatory Th17 cells. The objective of this proposal is to: Aim 1. To determine how STAT4 directs the accumulation of Th17 cells in inflamed peripheral tissues. Aim 2. To determine if the STAT4/IL-10 axis in Th17 cells governs chronic inflammation. Aim 3. To determine how STAT4 promotes pathogenic Th17 cell differentiation at the molecular level. Project Number: 1R01AI186373-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: Laurie Harrington | Institution: UNIVERSITY OF ALABAMA AT BIRMINGHAM, BIRMINGHAM, AL | Award Amount: $632,423 | Activity Code: R01 | Study Section: Mechanisms of Autoimmunity Study Section[MAI] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01AI18637301A1