Interleukin 17C (IL 17C) is a 15 20 kDa glycosylated cytokine that plays an important role in mucosal immunity and chronic inflammation. IL 17C binds to IL 17 RE with high affinity and to IL 17 RA with low affinity. These two receptor chains can associate into a heterodimeric receptor for IL 17C. IL 17C expression is induced by inflammatory stimulation in colon and airway epithelial cells, keratinocytes, CD4+ T cells, macrophages, and dendritic cells. It is up regulated in various chronic inflammatory diseases including psoriasis, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). IL 17 RE is reciprocally down regulated in psoriatic lesions. The interaction of IL 17C with IL 17 RE promotes mucosal immunity through the induction of anti bacterial peptides and pro inflammatory cytokines and chemokines. IL 17C action supports the integrity of the colon epithelium following infection induced damage but also contributes to psoriatic skin thickening and the progression of arthritis. IL 17C is additionally up regulated in Th17 cell dependent autoimmunity. In this setting, it exacerbates disease severity by inducing Th17 cell production of IL 17A, IL 17F, IL 22, CCR6, and CCL20.
The Interleukin-17 family proteins, comprising six members (IL-17, IL-17B through IL-17F),are secreted, structurally related proteins that share a conserved cysteine-knot fold near the C-terminus, but have considerable sequence divergence at the N-terminus. IL-17 family proteins are proinflammatory cytokines that induce local cytokine production and are involved in the regulation of immune functions. Among IL-17 family members, IL-17D is most closely related to IL-17B, sharing 27% aa sequence homology. IL-17D is expressed preferentially in skeletal muscle, heart, adipose tissue, lung, pancreas, and nervous system. Like other IL-17 family members, IL-17D modulates immune responses indirectly by stimulating the production of myeloid growth factors and chemokines including IL-6, IL-8, and GM-CSF. IL-17D has also been shown to suppress the proliferation of myeloid progenitors in colony formation assays.
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