IL10RB

IL10RB Full Name

interleukin 10 receptor, beta

IL10RB Introduction

Interleukin 10 Receptor, Beta (IL10RB), officially designated as interleukin 10 receptor subunit beta, is a protein-coding gene located on human chromosome 21q22.11, belonging to the class II cytokine receptor family. Also known by aliases such as CRFB4, IBD25, and IL-10R2, IL10RB encodes a crucial accessory chain that forms the active interleukin 10 (IL-10) receptor complex alongside IL10RA (interleukin 10 receptor subunit alpha). Unlike IL10RA, which is primarily responsible for ligand binding, IL10RB is constitutively expressed in most cell types and serves as the core signaling subunit, making its coexpression with IL10RA indispensable for IL-10-induced signal transduction and downstream biological effects. This receptor subunit is widely distributed across various tissues and cell populations, laying the foundation for its diverse roles in immune regulation and cellular homeostasis.

Figure 1. Crystal structure of IL-10 as published in the Protein Data Bank.

Functional Role in Cytokine Signaling and Immune Regulation
IL10RB is a critical mediator of immunomodulatory and antiviral signaling pathways. Its partnership with the ligand-binding chain IL10RA enables the formation of the functional IL-10 receptor complex, which triggers anti-inflammatory and immunosuppressive signals essential for limiting excessive immune responses and maintaining tissue homeostasis. When paired with IL22RA1 or IL20RB, IL10RB facilitates signaling by IL-22 or IL-26, which are involved in epithelial barrier defense, tissue repair, and mucosal immunity. Additionally, in conjunction with IL28RA, it forms receptors for interferon-λ cytokines, mediating antiviral responses particularly at epithelial surfaces.

Clinical and Translational Implications
Dysregulation or mutations in IL10RB are closely associated with several human diseases, primarily immune disorders and cancer. Homozygous loss-of-function mutations in IL10RB are a well-documented cause of very early onset inflammatory bowel disease (VEO-IBD), a severe form of IBD that presents in infancy or early childhood with symptoms such as intractable colitis, perianal fistulas, and growth faltering. These mutations abrogate IL-10 signaling by preventing STAT3 phosphorylation, leading to uncontrolled intestinal inflammation and impaired host defense. In cancer, IL10RB functions as a key regulator of tumor escape: its overexpression, often driven by the EMT (epithelial-mesenchymal transition) transcription factor Snail, enhances tumor cell invasion, adhesion, and chemoresistance by promoting invadopodium formation and inducing immune dysfunction in the tumor microenvironment. Specifically, high IL10RB expression in tumors reduces the number and cytotoxic activity of T cells and NK cells, creating an immunosuppressive microenvironment that facilitates tumor progression and treatment resistance.

Alternate Names for IL10RB

IL10RB; interleukin 10 receptor, beta; CRFB4, D21S58, D21S66; interleukin-10 receptor subunit beta; CDW210B; CRF2 4; IL 10R2; IL-10RB; IL-10R subunit 2; IL-10R subunit beta