Il17re, a part of the interleukin-17 receptor family, plays a crucial role in immune-mediated processes. Interleukin-17 (IL-17) cytokines bind to their receptors, including Il17re, activating intracellular signaling pathways that are involved in autoimmune diseases, inflammation, and host defense against pathogens [1,2,5]. The IL-17 signaling pathway, in which Il17re is implicated, has unique structural features distinguishing it from other cytokine families [1]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying Il17re function.

In a study using ApcMin mice colonized with enterotoxigenic Bacteroides fragilis (ETBF), it was found that the Bacteroides fragilis toxin (BFT) triggers a pro-carcinogenic inflammatory cascade that requires Il17re, NF-κB, and Stat3 signaling in colonic epithelial cells (CECs). This indicates that Il17re is involved in microbe-induced colon tumorigenesis [3]. In the KC-Tie2 inflammatory dermatitis mouse model, genetic elimination of Il17re, along with Il17c and Il17ra, reversed the increase in IL-17C and Zc3h12a and improved the skin phenotype, suggesting its role in skin inflammation [4].

In conclusion, Il17re is essential in immune-mediated processes, especially in inflammation and disease development. Findings from KO/CKO mouse models have revealed its role in colon tumorigenesis and skin inflammation. These studies contribute to understanding the mechanisms underlying diseases associated with dysregulated Il17re-mediated signaling, potentially guiding the development of new therapeutic strategies for related diseases.

References:

1. Gaffen, Sarah L. 2009. Structure and signalling in the IL-17 receptor family. In Nature reviews. Immunology, 9, 556-67. doi:10.1038/nri2586. https://pubmed.ncbi.nlm.nih.gov/19575028/

2. Berry, S P Déo-Gracias, Dossou, Camille, Kashif, Ali, Sabzvari, Araz, Zian, Zeineb. 2021. The role of IL-17 and anti-IL-17 agents in the immunopathogenesis and management of autoimmune and inflammatory diseases. In International immunopharmacology, 102, 108402. doi:10.1016/j.intimp.2021.108402. https://pubmed.ncbi.nlm.nih.gov/34863654/

3. Chung, Liam, Thiele Orberg, Erik, Geis, Abby L, Sears, Cynthia L, Housseau, Franck. 2018. Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells. In Cell host & microbe, 23, 203-214.e5. doi:10.1016/j.chom.2018.01.007. https://pubmed.ncbi.nlm.nih.gov/29398651/

4. Jiang, Yanyun, Gruszka, Dennis, Zeng, Chang, Gudjonsson, Johann E, Ward, Nicole L. 2024. Suppression of TCF4 promotes a ZC3H12A-mediated self-sustaining inflammatory feedback cycle involving IL-17RA/IL-17RE epidermal signaling. In JCI insight, 9, . doi:10.1172/jci.insight.172764. https://pubmed.ncbi.nlm.nih.gov/38470486/

5. Zhang, Qiaohui, Liao, Yan, Liu, Zhenquan, Li, Yue, Tang, Yibo. 2020. Interleukin-17 and ischaemic stroke. In Immunology, 162, 179-193. doi:10.1111/imm.13265. https://pubmed.ncbi.nlm.nih.gov/32935861/