Interleukin-21 receptor complex (IL-21R complex) (IL-21R complex)

The Interleukin-21 receptor complex (IL-21R complex) is a heterodimeric assembly consisting of the IL-21 receptor alpha subunit (IL-21R) and the common cytokine receptor gamma chain (CD132) [UniProt: Q9HBE5]. It is predominantly expressed on various immune cells, including B cells, T cells, and natural killer (NK) cells, playing a pivotal role in both innate and adaptive immunity [PubMed: 11163236]. Upon binding its ligand, IL-21, the receptor complex triggers the activation of the Janus kinase (JAK) signaling pathway, specifically involving JAK1, JAK3, and primarily STAT3 [PubMed: 15123770]. This signaling cascade is essential for the differentiation of B cells into antibody-secreting plasma cells and the formation of germinal centers, as well as the modulation of T-cell subsets like Th17 and T follicular helper (Tfh) cells [PubMed: 17110311]. In clinical contexts, overactivity of the IL-21R complex is linked to the development of autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), while its absence leads to severe combined immunodeficiency [PubMed: 21543662]. Therapeutic targeting of the IL-21R complex, primarily through monoclonal antibodies, aims to inhibit these inflammatory pathways in autoimmune and oncological conditions [ClinicalTrials.gov: NCT01206010].

Other names

IL-21RCD360NILRNovel interleukin receptorInterleukin-21 receptor subunit alphaIL-21R/IL-2RG complex

Antagonism of the IL-21R subunit to block ligand binding and subsequent recruitment of the common gamma chain, thereby inhibiting JAK1/JAK3-mediated STAT3 signaling.