IL17RA Gene

The IL17RA gene (IL17RA stands for "Interleukin-17 Receptor A") is a protein-coding gene located on chromosome 22q11. Alternative splicing of the gene results in multiple transcript variants encoding different isoforms.

"Interleukin-17 receptor A" encoded by the IL17RA gene has affinity for IL-17A and IL-17F, both important effector cytokines of the innate and adaptive immune systems. These interleukins are involved in antimicrobial host defense and maintenance of tissue integrity.

The IL17RA receptor protein also binds IL-17A and IL-17F homodimers as part of a heterodimeric complex with IL17RC. The receptor protein binds to IL-17A with higher affinity than to IL-17F. Cytokine binding triggers interaction of the complex with the TRAF3IP2 adaptor, leading to TRAF6-mediated activation of the NF-kappaB and MAP kinase signaling pathways. This ultimately leads to transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, resulting in a strong immune response.

This interleukin response pathway is involved in antimicrobial host defense, primarily by promoting the activation and recruitment of neutrophils at sites of infection to destroy extracellular bacteria and fungi. In secondary lymphoid organs, it contributes to the formation of germinal centers by regulating the chemotactic response of B cells to CXCL12 and CXCL13, promoting the retention of B cells within germinal centers, the somatic hypermutation rate of B cells and selection towards plasma cells. Furthermore, the IL-17RA/IL-17A/F/C complex plays a role in maintaining the integrity of epithelial barriers during homeostasis and pathogen infection. Stimulates the production of the antimicrobial beta-defensins DEFB1, DEFB103A and DEFB104A by mucosal epithelial cells, thereby limiting microbial invasion through the epithelial barriers. It is involved in antiviral host defense via various mechanisms.

Interleukin-17 receptor A is a receptor for the SARS coronavirus-2/SARS-CoV-2 viral protein ORF8, which leads to activation of the IL-17 signaling pathway and increased secretion of pro-inflammatory factors through activation of the NF-kappa-B signaling pathway.

Diseases associated with IL17RA include:

• Immunodeficiency 51 (Autosomal recessive inherited immunodeficiency caused by a defect in the interleukin-17 receptor A gene (IL17RA, 605461.0001) and characterized by a particular susceptibility to mucocutaneous candidiasis but also to staphylococcal infections (see below chronic mucocutaneous candidiasis).
• Psoriasis and psoriatic arthritis (Villalpando-Vargas FV et al. 2021).

1. Joob B et al (2020) Psoriasin and rs4819554 of IL-17RA gene polymorphism in psoriasis. Arch Dermatol Res 312:459.

2. Levy R et al (2016) Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency. Proc Nat Acad Sci 113: E8277-E8285.

3. Puel A et al (2011) Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332: 65-68.

4. Ramirez-Carrozzi V et al (2019) Cutting Edge: IL-17B Uses IL-17RA and IL-17RB to Induce Type 2 Inflammation from Human Lymphocytes. J Immunol 202:1935-1941
5. Villalpando-Vargas FV et al (2021) Association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to psoriasis and psoriatic arthritis: a meta-analysis. Inflamm Res 70:1201-1210.