Il17ra, encoding interleukin-17 receptor A, is a crucial component in the interleukin-17 signaling pathway. It serves as a common receptor for cytokines like IL-17A and IL-17F, and is involved in various biological processes including immune responses, cell growth, and differentiation. Dysregulation of the Il17ra-related pathway has implications in numerous diseases [1,2,5-10]. Genetic models, such as knockout (KO) mouse models, are valuable tools for studying its function.

In pancreatic cancer, deletion of Il17ra from the pancreatic epithelial compartment, but not the hematopoietic compartment, led to delayed initiation and progression of premalignant lesions and increased CD8+ cytotoxic T-cell infiltration, indicating that pancreatic epithelial Il17ra promotes pancreatic tumorigenesis by reprogramming the immune landscape, in part via B7-H4 regulation [1]. In Fanconi anemia, polymorphisms in the Il17ra gene were identified as risk factors for the disease, and were also associated with age and the presence of leukoplakia [2]. In ulcerative colitis, gingerenone A was shown to protect against the disease by directly interacting with Il17ra protein, inhibiting inflammatory signaling activation [3]. IL-17A-producing CD8+ T cells promoted pancreatic ductal adenocarcinoma (PDAC) via Il17ra-dependent stroma modification, accelerating tumor growth [4].

In conclusion, Il17ra plays essential roles in immune-related and disease-associated biological processes. Model-based research, especially the use of Il17ra KO mouse models, has significantly contributed to understanding its role in diseases such as pancreatic cancer, Fanconi anemia, and ulcerative colitis, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Castro-Pando, Susana, Howell, Rian M, Li, Le, Moghaddam, Seyed J, McAllister, Florencia. . Pancreatic Epithelial IL17/IL17RA Signaling Drives B7-H4 Expression to Promote Tumorigenesis. In Cancer immunology research, 12, 1170-1183. doi:10.1158/2326-6066.CIR-23-0527. https://pubmed.ncbi.nlm.nih.gov/38842383/

2. Mobile, Rafael Zancan, Mendes, Monalisa Castilho, Machado-Souza, Cleber, Torres-Pereira, Cassius Carvalho, Schussel, Juliana Lucena. 2023. IL17A and IL17RA gene polymorphisms in Fanconi anemia. In Brazilian oral research, 37, e012. doi:10.1590/1807-3107bor-2023.vol37.0012. https://pubmed.ncbi.nlm.nih.gov/36790253/

3. Liang, Jian, Dai, Weigang, Liu, Chuanghui, Wang, Wei, Tang, Hailin. 2024. Gingerenone A Attenuates Ulcerative Colitis via Targeting IL-17RA to Inhibit Inflammation and Restore Intestinal Barrier Function. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2400206. doi:10.1002/advs.202400206. https://pubmed.ncbi.nlm.nih.gov/38639442/

4. Picard, Felix Simon Ruben, Lutz, Veronika, Brichkina, Anna, Gaida, Matthias, Huber, Magdalena. 2023. IL-17A-producing CD8+ T cells promote PDAC via induction of inflammatory cancer-associated fibroblasts. In Gut, 72, 1510-1522. doi:10.1136/gutjnl-2022-327855. https://pubmed.ncbi.nlm.nih.gov/36759154/