Il17b-KO Mouse

Il17b is a member of the interleukin-17 (IL-17) family of cytokines. The IL-17 family consists of six members (IL-17A to IL-17F), and Il17b signals through the Il17b-Il17RB pathway. While the functions of some IL-17 family members like IL-17A in autoimmunity, inflammation, etc., are well-studied, the functions of Il17b were once largely elusive but are now being increasingly understood [1,2,3,7,8].

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 resulted in increased neutrophil infiltration and enhanced inflammatory cytokines in intestinal macrophages in colitis [6]. In injured peripheral nerves, global or Schwann-cell-specific Il17b deletion reduced macrophage infiltration, myelin clearance, and axon regeneration, indicating its role in Schwann-cell-mediated macrophage recruitment through the Il17B/Il17RB pathway [4]. In bleomycin-induced mouse lung fibrosis, either lung-microbiota depletion or Il17b deficiency ameliorated disease progression, suggesting that dysregulated lung commensal bacteria-driven Il17b production promotes pulmonary fibrosis [5].

In conclusion, Il17b plays important roles in multiple biological processes and disease conditions. Through gene knockout (KO) and conditional knockout (CKO) mouse models, its functions in colitis, peripheral nerve injury, and pulmonary fibrosis have been revealed. These findings contribute to our understanding of the underlying mechanisms in these disease areas and may provide potential therapeutic targets.

References:

1. Iwakura, Yoichiro, Ishigame, Harumichi, Saijo, Shinobu, Nakae, Susumu. . Functional specialization of interleukin-17 family members. In Immunity, 34, 149-62. doi:10.1016/j.immuni.2011.02.012. https://pubmed.ncbi.nlm.nih.gov/21349428/

2. Brembilla, Nicolo Costantino, Senra, Luisa, Boehncke, Wolf-Henning. 2018. The IL-17 Family of Cytokines in Psoriasis: IL-17A and Beyond. In Frontiers in immunology, 9, 1682. doi:10.3389/fimmu.2018.01682. https://pubmed.ncbi.nlm.nih.gov/30127781/

3. Brembilla, Nicolo Costantino, Boehncke, Wolf-Henning. 2023. Revisiting the interleukin 17 family of cytokines in psoriasis: pathogenesis and potential targets for innovative therapies. In Frontiers in immunology, 14, 1186455. doi:10.3389/fimmu.2023.1186455. https://pubmed.ncbi.nlm.nih.gov/37283755/

4. Huang, Yanju, Wu, Liwen, Zhao, Yueshan, Ma, Suchen, Ying, Zhengxin. 2024. Schwann cell promotes macrophage recruitment through IL-17B/IL-17RB pathway in injured peripheral nerves. In Cell reports, 43, 113753. doi:10.1016/j.celrep.2024.113753. https://pubmed.ncbi.nlm.nih.gov/38341853/

5. Yang, Daping, Chen, Xi, Wang, Jingjing, Song, Xinyang, Qian, Youcun. 2019. Dysregulated Lung Commensal Bacteria Drive Interleukin-17B Production to Promote Pulmonary Fibrosis through Their Outer Membrane Vesicles. In Immunity, 50, 692-706.e7. doi:10.1016/j.immuni.2019.02.001. https://pubmed.ncbi.nlm.nih.gov/30824326/

6. Zhang, Xiaomin, Zhang, Xiaokai, Song, Xiaomei, Guo, Hong, Shi, Yun. 2023. Interleukin 17 B regulates colonic myeloid cell infiltration in a mouse model of DSS-induced colitis. In Frontiers in immunology, 14, 1055256. doi:10.3389/fimmu.2023.1055256. https://pubmed.ncbi.nlm.nih.gov/36814913/

7. Taams, Leonie S, Steel, Kathryn J A, Srenathan, Ushani, Burns, Lachrissa A, Kirkham, Bruce W. . IL-17 in the immunopathogenesis of spondyloarthritis. In Nature reviews. Rheumatology, 14, 453-466. doi:10.1038/s41584-018-0044-2. https://pubmed.ncbi.nlm.nih.gov/30006601/

8. Paek, So Yeon, Frieder, Jillian, Kivelevitch, Dario, Menter, M Alan. . IL-17 inhibitors for psoriasis. In Seminars in cutaneous medicine and surgery, 37, 148-157. doi:10.12788/j.sder.2018.051. https://pubmed.ncbi.nlm.nih.gov/30215631/