Interleukin-10 receptor and Transforming growth factor beta receptor (IL-10R/TGF-βR)

The target entry refers to a dual-signaling interface involving the Interleukin-10 receptor (IL-10R) and the Transforming growth factor beta receptor (TGF-βR) on effector immune cells and antigen-presenting cells (APCs). These receptors are critical regulators of immune homeostasis; IL-10R signaling typically activates the JAK1/STAT3 pathway to mediate anti-inflammatory effects, while TGF-βR signaling through SMAD proteins is a primary driver of immunosuppression and fibrosis (Moore et al., 2001; Massagué, 2000). In the tumor microenvironment, TGF-β promotes immune evasion by inducing regulatory T cell differentiation and inhibiting the cytotoxic activity of CD8+ T cells and Natural Killer cells (Batlle & Massagué, 2019). Conversely, IL-10 can have complex roles, often acting to suppress the maturation of APCs and the production of pro-inflammatory cytokines like IL-12. Therapeutic strategies targeting this axis include bifunctional fusion proteins, such as Bintrafusp alfa, which sequesters TGF-β while targeting PD-L1, and recombinant IL-10 variants like Pegilodecakin designed to stimulate anti-tumor immunity. The clinical challenge in modulating these receptors lies in their pleiotropic nature, where systemic interference can lead to significant toxicities such as skin lesions or severe inflammatory responses.

Other names

IL10RTGFBRIL-10 and TGF-beta signaling axisInterleukin-10 receptor complexTransforming growth factor beta receptor complex

Simultaneous or coordinated modulation of the IL-10 and TGF-β signaling pathways to alter the activation state of effector immune cells and antigen-presenting cells.