Role of NOD2 signaling and molecular mechanisms involved in the generation of IL-17 pathogenic T cells in autoimmune diseases

• Grant number: 12/14924-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 30, 2012
• End date: November 29, 2013
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Fernando de Queiroz Cunha
• Grantee: Rafael Freitas de Oliveira Franca
• Supervisor: Vijay K. Kuchroo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 10/19770-2 - Characterization of endogenous NOD2 agonist isolated from synovial fluids of patients with rheumatoid arthritis., BP.PD

Abstract

There are a consensus about the existence of two subpopulations of Th17 T cells, the so called "classical Th17" and a second population denominated "alternative Th17 cells". The alternative Th17 cells are characterized as a highly pathogenic subpopulation and it is related with the development of autoimmune diseases. In this context, Prof. Vijay K. Kuchroo group has demonstrated the participation of several molecular mechanisms in the generation of pathogenic Th17 T cells. Interestingly, the cited group recently identified the participation of a protein denominated Serum and Glucocorticoid Induced Kinase-1 (SGK1), to be specifically induced in T regulatory T cells (Tregs) and Th17 cells, contributing to the emergence of pathogenic Th17 responses and inhibiting the function of Tregs. Our research group recently demonstrated that NOD2 deficient mice are resistant to experimental arthritis, in a model of antigen induced arthritis. In this model, we observed decreased levels of IL-1², IL-23 and IL-6, reduction in neutrophil recruitment and cartilage degradation with consequent disease reduction. Although these evidences indicate the involvement of NOD2 in the pathogenesis of several autoimmune diseases, the mechanisms by which this receptor participates in the inflammatory process are not clearly established. Considering NOD2 signaling pathway as an important mechanism to Th17 T cell generation, mainly through the induction of cell differentiating factors such as IL-23, IL-6 and IL-1², we propose to study at the molecular level, the events involved in NOD2 signaling as well the molecular events that participates in the generation process of pathogenic Th17 T cells, leading to autoimmune diseases such as rheumatoid arthritis. (AU)

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)

WU, CHUAN; THALHAMER, THERESA; FRANCA, RAFAEL F.; XIAO, SHENG; WANG, CHAO; HOTTA, CHIE; ZHU, CHEN; HIRASHIMA, MITSUOMI; ANDERSON, ANA C.; KUCHROO, VIJAY K.. Galectin-9-CD44 Interaction Enhances Stability and Function of Adaptive Regulatory T Cells. IMMUNITY, v. 41, n. 2, p. 270-282, AUG 21 2014. (12/14924-7)