Interleukin-20 receptor type I (IL-20R1/IL-20R2)

The IL-20R1/IL-20R2 heterodimer, also known as the Type I IL-20 receptor, is a transmembrane protein complex belonging to the Class II cytokine receptor family [2, 4]. It is composed of two subunits: the interleukin-20 receptor subunit alpha (IL-20R1 or IL-20RA) and the interleukin-20 receptor subunit beta (IL-20R2 or IL-20RB) [2, 11]. This receptor complex is primarily expressed on non-hematopoietic cells, such as keratinocytes, epithelial cells, and fibroblasts, and serves as a functional receptor for the IL-20 subfamily cytokines, including IL-19, IL-20, and IL-24 [4, 7, 11]. Upon ligand binding, the receptor activates the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, particularly STAT3, which regulates genes involved in inflammation, cell proliferation, and tissue repair [8, 11]. Dysregulation of IL-20R1/IL-20R2 signaling is strongly implicated in the pathogenesis of chronic inflammatory diseases like psoriasis and rheumatoid arthritis, as well as in bone loss and certain cancers [5, 6, 9, 13]. Therapeutic strategies targeting this receptor or its ligands, such as monoclonal antibodies like fletikumab, aim to dampen the excessive inflammatory response and have been explored in clinical trials for autoimmune conditions [24, 33]. While targeting this pathway offers therapeutic potential, challenges include the redundancy of the Type II IL-20 receptor and the potential for increased susceptibility to certain infections, as these cytokines play a role in maintaining epithelial barrier integrity [18, 43].

Other names

Type I IL-20 receptorIL-20RA/IL-20RB complexIL-20R1/R2ZCYTOR7/FNDC6 complex

Antagonism of the receptor complex or neutralization of its ligands (IL-19, IL-20, IL-24) to inhibit the JAK/STAT3 signaling pathway, thereby reducing the production of pro-inflammatory cytokines and mediators.