Il17f-KO Mouse

Il17f, Interleukin 17F, is a cytokine belonging to the IL-17 family. It has been implicated in various inflammatory pathologies, playing roles in chronic inflammation, autoimmunity, and host defense against microbial organisms [6,7]. IL-17A and IL-17F, which have certain overlapping functions, signal mainly through activation of the nuclear factor-kappa B (NF-κB) pathway and are involved in controlling bacterial and fungal infections [6].

IL17F gene expression can be induced by oxidative stress-related stressors like aqueous cigarette smoke extract, inorganic mercury, cadmium, or brefeldin A in various cell lines, and this induction is associated with cytotoxic/apoptotic signs [1]. In the context of diseases, IL17F rs763780 polymorphism is associated with asthma after bronchiolitis in infancy, as children with the variant genotype had more use of inhaled corticosteroids and higher incidence of atopic dermatitis [3]. In HLA-B*27 negative Brazilian patients, the IL17F C allele frequency was higher in those with spondyloarthritis, suggesting it could be a risk marker [5]. Bimekizumab, a monoclonal antibody inhibiting both IL-17A and IL-17F, shows better skin clearance than secukinumab (which inhibits only IL-17A) in moderate-to-severe plaque psoriasis patients, though it is associated with more oral candidiasis [2]. Similarly, in comparison with adalimumab, bimekizumab is more effective in reducing symptoms of plaque psoriasis but also has a higher frequency of oral candidiasis and diarrhea [4].

In conclusion, Il17f is significantly involved in inflammatory and autoimmune-related diseases. Research on Il17f, including studies using genetic models (implied by polymorphism studies), has provided insights into its role in asthma, spondyloarthritis, and psoriasis, suggesting it could be a potential therapeutic target in these disease areas.

References:

1. Bauer, Mario, Fink, Beate, Anderegg, Ulf, Röder, Stefan, Zenclussen, Ana Claudia. 2022. IL17F Expression as an Early Sign of Oxidative Stress-Induced Cytotoxicity/Apoptosis. In Genes, 13, . doi:10.3390/genes13101739. https://pubmed.ncbi.nlm.nih.gov/36292624/

2. Reich, Kristian, Warren, Richard B, Lebwohl, Mark, Peterson, Luke, Blauvelt, Andrew. 2021. Bimekizumab versus Secukinumab in Plaque Psoriasis. In The New England journal of medicine, 385, 142-152. doi:10.1056/NEJMoa2102383. https://pubmed.ncbi.nlm.nih.gov/33891380/

3. Holster, Annukka, Teräsjärvi, Johanna, Barkoff, Alex-Mikael, He, Qiushui, Nuolivirta, Kirsi. 2020. IL17F rs763780 single nucleotide polymorphism is associated with asthma after bronchiolitis in infancy. In Acta paediatrica (Oslo, Norway : 1992), 110, 222-227. doi:10.1111/apa.15390. https://pubmed.ncbi.nlm.nih.gov/32495451/

4. Warren, Richard B, Blauvelt, Andrew, Bagel, Jerry, Cross, Nancy, Reich, Kristian. 2021. Bimekizumab versus Adalimumab in Plaque Psoriasis. In The New England journal of medicine, 385, 130-141. doi:10.1056/NEJMoa2102388. https://pubmed.ncbi.nlm.nih.gov/33891379/

5. Neves, Janisleya Silva Ferreira, Visentainer, Jeane Eliete Laguila, Reis, Denise Manjurma da Silva, Zacarias, Joana Maira Valentini, Sell, Ana Maria. 2021. IL17F: A Possible Risk Marker for Spondyloarthritis in HLA-B*27 Negative Brazilian Patients. In Journal of personalized medicine, 11, . doi:10.3390/jpm11060520. https://pubmed.ncbi.nlm.nih.gov/34200121/

6. Navarro-Compán, Victoria, Puig, Luis, Vidal, Silvia, Queiro, Rubén, Cañete, Juan D. 2023. The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases. In Frontiers in immunology, 14, 1191782. doi:10.3389/fimmu.2023.1191782. https://pubmed.ncbi.nlm.nih.gov/37600764/

7. Sánchez-Rodríguez, Guillermo, Puig, Lluís. 2023. Pathogenic Role of IL-17 and Therapeutic Targeting of IL-17F in Psoriatic Arthritis and Spondyloarthropathies. In International journal of molecular sciences, 24, . doi:10.3390/ijms241210305. https://pubmed.ncbi.nlm.nih.gov/37373452/