Interleukin-6 receptor subunit alpha (IL-6R) (IL-6R)

The Interleukin-6 receptor subunit alpha (IL-6R) is a type I cytokine receptor that mediates the pleiotropic biological effects of Interleukin-6 (IL-6), a central regulator of the immune system and the acute phase response [1, 3]. The receptor exists in both a membrane-bound form (mIL-6R) and a soluble form (sIL-6R); both forms can bind IL-6 and subsequently recruit the signal-transducing protein gp130 to form a hexameric signaling complex [2, 6]. This complex activates several intracellular pathways, most notably the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, which drives the expression of genes involved in inflammation and cell survival [3, 8]. Dysregulation of IL-6R signaling is implicated in the pathogenesis of various autoimmune and inflammatory disorders, including rheumatoid arthritis, Castleman disease, and cytokine release syndrome [4, 11, 12]. Therapeutic strategies targeting the IL-6R include monoclonal antibodies such as tocilizumab and sarilumab, which competitively inhibit IL-6 binding and effectively suppress both classic and trans-signaling pathways [7, 9, 10]. While these treatments are highly effective in managing chronic inflammation, they are associated with significant safety concerns, including an increased risk of serious infections, gastrointestinal perforation, and hematological abnormalities [12, 13].

Other names

CD126gp80IL-6R-alphaInterleukin-6 receptor subunit alphaIL-6RA

Competitive inhibition of Interleukin-6 binding to the Interleukin-6 receptor subunit alpha, which prevents the formation of the signaling-active hexameric complex with gp130 and blocks downstream activation of the JAK-STAT, MAPK, and PI3K/Akt pathways [1, 3, 12].