Interleukin-17 receptor A (IL17RA) (IL17RA)

Interleukin-17 receptor A (IL17RA) is a ubiquitous transmembrane protein that functions as a critical signaling component of the IL-17 receptor family. It forms heterodimeric complexes with other IL-17 receptor subunits, such as IL17RC or IL17RE, to bind various IL-17 cytokine isoforms including IL-17A, IL-17F, and IL-17E (IL-25) [UniProt, https://www.uniprot.org/uniprotkb/Q96F46/entry]. Upon ligand binding, IL17RA initiates a pro-inflammatory signaling cascade involving Act1 and TRAF6, leading to the activation of NF-kappa-B and MAP kinase pathways which drive the expression of inflammatory cytokines and chemokines [NCBI Gene, https://www.ncbi.nlm.nih.gov/gene/23765]. Pathologically, overactive IL17RA signaling is a primary driver of chronic inflammatory conditions such as plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. Brodalumab is a clinically approved monoclonal antibody that directly targets the IL17RA protein to inhibit these inflammatory pathways [DrugBank, https://go.drugbank.com/drugs/DB09057]. While the protein is the established therapeutic target, the IL17RA mRNA transcript is also an object of interest for RNA-based therapies, such as siRNA or antisense oligonucleotides, aimed at reducing receptor expression at the pre-translational level to treat localized inflammatory skin diseases [PubMed, https://pubmed.ncbi.nlm.nih.gov/23812244/]. Blocking IL17RA is highly effective in treating psoriasis but requires monitoring for safety concerns such as fungal infections and mood changes [FDA, https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761032lbl.pdf].

Other names

CD217IL17RCANDF5hIL-17RInterleukin-17 receptor A mRNA

Brodalumab is a human monoclonal antibody that binds with high affinity to the IL17RA subunit, thereby blocking the biological activity and downstream signaling of pro-inflammatory cytokines including IL-17A, IL-17F, IL-17A/F heterodimers, and IL-17E (IL-25). For mRNA-targeted modalities, experimental therapies such as siRNA or antisense oligonucleotides are designed to bind the IL17RA mRNA transcript to induce its degradation or inhibit translation, effectively reducing the density of the receptor on the cell surface.