Interleukin-10 receptor complex (IL-10R) (IL-10R)

The Interleukin-10 receptor (IL-10R) complex is a heterotetrameric cytokine receptor composed of two high-affinity alpha subunits (IL-10RA or IL-10R1) and two accessory beta subunits (IL-10RB or IL-10R2) [2.1.1, 2.1.3]. It belongs to the Class II cytokine receptor family and is primarily expressed on hematopoietic cells such as macrophages, monocytes, and lymphocytes [2.1.1, 2.3.1]. Upon binding its ligand, Interleukin-10 (IL-10), the receptor complex recruits and activates Janus kinases (JAK1 and TYK2), which subsequently phosphorylate the signal transducer and activator of transcription 3 (STAT3) [2.1.3, 2.2.2]. This signaling pathway is a master regulator of anti-inflammatory responses, inhibiting the production of pro-inflammatory cytokines like TNF-alpha, IL-1, and IL-6 [2.1.1, 2.3.1]. Mutations in the IL-10R subunits are strongly associated with very early-onset inflammatory bowel disease (VEO-IBD), underscoring its role in maintaining mucosal homeostasis [2.1.3, 2.2.2]. In clinical development, the IL-10R complex is targeted by agonists such as pegilodecakin (AM0010) to stimulate anti-tumor CD8+ T cell activity, while inhibitors are being explored to counteract immunosuppression in chronic infections and cancer [3.2.1, 3.2.3]. Therapeutic challenges include managing systemic side effects like anemia and balancing the complex's dual roles in immune regulation [2.4.2, 3.3.3].

Other names

IL10RInterleukin-10 receptorIL-10 receptor complexCD210IL10RA/IL10RB complexInterleukin-10 receptor subunit alphaInterleukin-10 receptor subunit betaCD210aCDw210aHIL-10RIL-10R1IL-10R2CRF2-4CRFB4

Agonism of the IL-10 receptor complex activates the JAK1/TYK2/STAT3 signaling pathway, leading to the transcription of anti-inflammatory genes and the invigoration of CD8+ T cells. Antagonism or neutralization of the pathway blocks these immunosuppressive effects to enhance anti-tumor or anti-pathogen immune responses.