The IL-17 Cytokine Family

IL-17A and its receptor are the founding members of a recently described cytokine family, with unique sequences and functions in the immune system and elsewhere. Consisting of six ligands (IL-17A-F) and five receptors (IL-17RA-IL-17RE) in mammals, these molecules have distinct primary amino acid structures with only minimal homology to other cytokine families. By far the best studied of these cytokines to date are IL-17A and its receptor, IL-17RA. IL-17A is produced primarily by T cells, and is the hallmark cytokine of a newly defined T helper cell subset that appears to be involved in generation of autoimmunity. Despite its production by the adaptive immune system, IL-17A exhibits proinflammatory activities similar to innate immune cytokines such as IL-1β and TNF-α and appears to play important and nonredundant roles in regulating granulocytes in vivo. As a result, IL-17A also plays key roles in host defense. In contrast to the restricted expression of IL-17A, the IL-17RA receptor is ubiquitously expressed, and thus most cells are potential physiological targets of IL-17A. This chapter describes the major molecular properties, biological activities, and known signaling pathways of the IL-17 family, with an emphasis on IL-17A and IL-17RA.