Th 17 Cells: Role in Inflammation and Autoimmune Disease

The IL-17 cytokines represent a novel family of cytokines, which defines a new effector T cell, the Th17 cell, and extend the Th1-Th2 paradigm. Th17 cells in part co-express at least IL-17A and IL-17F, IL-21 and IL-22. IL-17 A/F are produced by T cells ( and ), iNKT cells, and possibly neutrophils, dendritic cells and Paneth cells. The regulation of IL-17 family members expression, and the identification of effector mechanisms are an area of intense current research. Recognized regulators of IL-17A expression include the nuclear receptor ROR t, proinflammatory cyt- ines such as IL-1, IL-6 with TGF- , IL-21, IL-23 IL-25 in the absence of IFN- and IL-4, which are discussed. Recent data suggest that IL-17A may have a dual fu- tion pro-inflammatory and anti-inflammatory- suggesting that IL-17A may also contribute to terminate inflammation. Further, a reciprocal regulation of Th17 and regulatory T cells including the role of retinoic acid and TGF- is discussed. The discovery that patients with rheumatoid arthritis, allergic disorders, psor- sis and inflammatory bowel disease express IL-17A generated interest in the medical community and instigated a flurry of experimental research on the potential role of Th17 in inflammatory diseases. Experimental studies confirmed that IL-17A is induced and is critical for the development of allergic lung inflammation, arthritis, bacterial sepsis, experimental allergic encephalomyelitis and myocarditis, as well as other inflammatory con- tions including organ transplantation. The role of IL-17F and IL-22 is still poorly defined and is only slowly emerging.