Interleukin 17

Interleukin 17 (IL-17 or IL-17A) is a homodimeric glycoprotein with a molecular mass of about 35 KDa belonging to a family of unique cytokines intimately involved in various immune/autoimmune related diseases including asthma and rheumatoid arthritis.

The family members include IL-17B, IL-17C, IL-17D, IL-17E (also known as IL-25) and IL-17F. The members resemble each other by similar protein structures with four highly conserved cysteine residues. This structural resemblance, however, is not reflected in their amino acid sequences that vary from 17 to 55%.

IL-17 elicits its function by binding to a type 1 cell surface receptor (IL-17R) inducing the production of many other cytokines, chemokines and prostaglandins such as IL-6, IL-8, MCP-1, G-CSF, GM-CSF, IL-1β, TGF-β, TNF-α and PGE2.
Originally IL-17 production was reported to be dependent on IL-23 but later studies revealed that IL-17 could be induced by other cytokines such as IL-6 and TGF-β.

IL-17 function is also essential to a subset of CD4+ T cells, called T helper IL-17 (Th17) cells. Th17 cells express CCR4, CCR6 and STAT4 and are clearly pathogenic, thereby challenging the importance of classical Th1 cells in the induction and maintenance of chronic inflammatory disease.  As a result of these properties, the IL-17 family has been linked to various immune/autoimmune related diseases including rheumatoid arthritis, asthma, lupus, allograft rejection and anti-tumor immunity.

The individual contributions of the two most closely related members (IL-17A and IL-17F; sharing 55% homology at the amino acid level) have been an area of intense research in the past several years. Most evidence to date indicates that IL-17A is more critical than IL-17F in mediating experimental autoimmunity. Distinct functions for IL-17A and IL-17F in mediating inflammation resulting from mucosal infection and autoimmune processes have been demonstrated. Most puzzling in these studies was the question why cytokines, with such similar structures and properties and signaling through the same receptors (IL-17RA and IL-17RC), exert such distinct functions in vitro and in vivo.