Chapter 6 - Role of Th17 cell in tissue inflammation and organ-specific autoimmunity

Abstract

IL-17-producing T helper (Th) 17 cells have been shown to be involved in the pathogenesis of a variety of inflammatory and autoimmune diseases like multiple sclerosis (MS), psoriasis, and inflammatory bowel disease (IBD). Understanding the molecular basis of the induction of pathogenic Th17 cells during tissue inflammation is critical in targeting cytokines, cytokine receptors, and transcription factors that enhance the pathogenic functions of Th17 cells. Neutralization of IL-17 by anti-IL-17 antibody has shown a great therapeutic potential in psoriasis. However, pathogenic Th17 cells also express other cytokines like granulocyte macrophage-colony stimulating factor (GM-SCF), IL-17F, IL-22, and IL-26, which may also contribute to the tissue inflammation in different autoimmune diseases. Therefore, targeting one cytokine at a time may not be useful to tackle Th17 cell-mediated diseases. It is, therefore, imperative to block Th17 cell generation or targeting the factors that drive the generation of pathogenic Th17 cells. Retinoid-related orphan receptor-γt (RORγt) and IL-23-IL-23R axis are the two major checkpoints in the development of pathogenic Th17 cells. Blocking RORγt using small molecules inhibitors or inhibiting IL-23 function by blocking the cytokine and its receptor have shown promising benefits preclinically. In this chapter, biology and recent advances in targeted therapy that block Th17 cells-mediated tissue inflammation in autoimmune diseases are discussed.