Interleukin-17C (IL‑17C) is a 15‑20 kDa glycosylated cytokine that plays an important role in mucosal immunity and chronic inflammation. The six IL‑17 cytokines (IL‑17A‑F) are encoded by separate genes but adopt a conserved cystine knot fold (1, 2). Mature mouse IL‑17C shares 79% and 95% amino acid sequence identity with human and rat IL‑17C, respectively (3). IL‑17C binds to IL‑17 RE with high affinity and to IL‑17 RA with low affinity (4, 5). These two receptor chains can associate into a heterodimeric receptor for IL‑17C (4‑6). IL-17 RE is expressed on keratinocytes, mucosal epithelial cells, Th17 cells, and gamma /δ T cells, while IL-17 RA is widely expressed (4, 5). IL‑17 RE is required for mediating the pro-inflammatory and homeostatic actions of IL‑17C in the skin and mucosa (1, 2). IL‑17C expression is induced by inflammatory stimulation in colon and airway epithelial cells, keratinocytes, CD4 ⁺ T cells, macrophages, and dendritic cells (4, 6‑9). It is up‑regulated in various chronic inflammatory diseases including psoriasis, cystic fibrosis, and chronic obstructive pulmonary disease (COPD) (7  8, 10). IL‑17 RE is reciprocally downregulated in psoriatic lesions (10). 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 (4, 6, 8, 9). IL‑17C action supports the integrity of the colon epithelium following infection induced damage (4, 6, 11) but also contributes to psoriatic skin thickening and the progression of arthritis (4,8, 9). IL‑17C is additionally up‑regulated in Th17 cell dependent autoimmunity (5). In this setting, it exacerbates disease severity by inducing Th17 cell production of IL‑17A, IL‑17F, IL‑22, CCR6, and CCL20 (5).