Il17a-KO Mouse

IL17A, a major member of the IL-17 cytokine family, is mainly produced by T helper 17 (Th17) cells, along with other cell types such as CD8+ T cells, γδ T cells, etc. It has host-protective capacity in healthy individuals, but excessive elevation is linked to autoimmune diseases and cancer. It is involved in immune responses, especially in the pathogenesis of diseases like chronic obstructive pulmonary disease (COPD), spondyloarthritis, and psoriasis [2,4]. Genetic models, especially knockout (KO) mouse models, have been crucial in understanding its functions.

In a COPD mouse model, selective knockout of IL17A in the airway epithelium significantly reduced neutrophilic infiltration, peribronchial inflammation, pro-inflammatory mediators, and mucus production, indicating that epithelium-derived IL17A can act in an autocrine manner to amplify inflammation and increase mucus production in COPD pathogenesis [1]. In HLA-B27 transgenic rats, a peptide-based vaccine targeting IL17A alleviated the spondyloarthritis (SpA) phenotype, inhibiting enthesitis, bone destruction, and new bone formation, suggesting the importance of IL17A in SpA [3].

In conclusion, IL17A plays a key role in immune-mediated inflammatory processes. KO mouse models and related functional studies have revealed its significance in diseases such as COPD and SpA. Understanding IL17A's functions can provide new insights into the pathogenesis of these diseases and potential therapeutic strategies.

References:

1. Wu, Mindan, Lai, Tianwen, Jing, Du, Wu, Xiaohong, Shen, Huahao. . Epithelium-derived IL17A Promotes Cigarette Smoke-induced Inflammation and Mucus Hyperproduction. In American journal of respiratory cell and molecular biology, 65, 581-592. doi:10.1165/rcmb.2020-0424OC. https://pubmed.ncbi.nlm.nih.gov/34186014/

2. McGonagle, Dennis G, McInnes, Iain B, Kirkham, Bruce W, Sherlock, Jonathan, Moots, Robert. 2019. The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies. In Annals of the rheumatic diseases, 78, 1167-1178. doi:10.1136/annrheumdis-2019-215356. https://pubmed.ncbi.nlm.nih.gov/31278139/

3. Hayashi, Hiroki, Sun, Jiao, Yanagida, Yuka, Tomita, Tetsuya, Nakagami, Hironori. . Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic rats. In RMD open, 9, . doi:10.1136/rmdopen-2022-002851. https://pubmed.ncbi.nlm.nih.gov/36737108/

4. Song, Meiying, Liang, Jie, Wang, Luoyang, Zhang, Li, Zhang, Bei. 2023. IL-17A functions and the therapeutic use of IL-17A and IL-17RA targeted antibodies for cancer treatment. In International immunopharmacology, 123, 110757. doi:10.1016/j.intimp.2023.110757. https://pubmed.ncbi.nlm.nih.gov/37579542/