Interleukin-10 and Interleukin-35 signaling pathway

The Interleukin-10 (IL-10) and Interleukin-35 (IL-35) signaling pathway is a critical mechanism used by regulatory T cells (Tregs) to maintain immune homeostasis and promote infectious tolerance [3, 5]. This pathway suppresses the activity of both antigen-specific effector T cells and non-specific bystander T cells in the local environment [4]. IL-10 functions by binding to its receptor complex (IL-10RA/IL-10RB), which triggers STAT3 phosphorylation and leads to the downregulation of pro-inflammatory cytokines and MHC class II molecules [1]. IL-35, a heterodimeric cytokine composed of EBI3 and IL-12p35, signals through various receptor combinations (e.g., IL-12Rβ2/gp130) to induce the conversion of target T cells into a regulatory phenotype known as iTr35 cells [2, 3]. In oncology, tumors often exploit this signaling axis to evade immune surveillance, while its dysfunction is linked to the development of autoimmune and inflammatory diseases [5]. Therapeutic interventions include IL-10 agonists like pegilodecakin for chronic inflammation and experimental antagonists targeting IL-10 or IL-35 to enhance anti-tumor immunity.

Other names

Treg-mediated suppressionInfectious toleranceBystander T cell suppressionIL-10/IL-35 inhibitory axisRegulatory T cell signaling

Activation of STAT3 via the IL-10 receptor and STAT1/STAT4 via the IL-35 receptor to induce immune suppression and infectious tolerance.