Il17b is a member of the interleukin-17 (IL-17) family, which consists of six members (IL-17A to IL-17F). While the functions of some IL-17 family members are well-defined, the role of Il17b was once elusive. It is involved in multiple biological processes and disease-related pathways, and its study using genetic models like knockout (KO) mouse models can help clarify its functions [1].

In a mouse model of DSS-induced colitis, Il17b deficiency led to severe colitis with exaggerated weight loss, shorter colon length, and elevated proinflammatory cytokines in the colon. Recombinant IL-17B treatment alleviated the severity of colitis. Single-cell transcriptional analyses showed that loss of Il17b increased neutrophil infiltration and enhanced inflammatory cytokines in intestinal macrophages [4]. In injured peripheral nerves, Schwann-cell-secreted Il17b binds to IL-17 receptor B in an autocrine manner to promote macrophage recruitment. Global or Schwann-cell-specific Il17b deletion reduced macrophage infiltration, myelin clearance, and axon regeneration [2]. In bleomycin-induced mouse lung fibrosis, the dysregulated lung microbiota induced Il17b production. Either lung-microbiota depletion or Il17b deficiency ameliorated disease progression [3].

In conclusion, Il17b plays important roles in multiple biological processes such as macrophage recruitment in injured peripheral nerves, regulation of colonic myeloid cell infiltration in colitis, and in the pathogenesis of pulmonary fibrosis. The use of Il17b KO mouse models has been crucial in revealing its functions in these specific disease-related processes, providing insights into potential therapeutic targets for conditions like colitis, nerve injury, and pulmonary fibrosis.