Interleukin-10 signaling pathway (IL-10 pathway)

The Interleukin-10 (IL-10) signaling pathway is a fundamental anti-inflammatory cascade essential for maintaining immune homeostasis and preventing immunopathology. The pathway is initiated by the binding of the homodimeric IL-10 cytokine to its heterotetrameric receptor complex, consisting of IL-10RA and IL-10RB subunits, which triggers the activation of Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2). These kinases subsequently phosphorylate the signal transducer and activator of transcription 3 (STAT3), leading to its nuclear translocation and the induction of an anti-inflammatory gene program that suppresses the production of pro-inflammatory cytokines such as TNF-alpha, IL-1, and IL-6. Beyond its primary anti-inflammatory role, the pathway also influences B cell survival and T cell regulation, and it exhibits a complex, dual role in cancer by either promoting or inhibiting tumor growth depending on the microenvironment. Therapeutic modulation of this pathway includes the use of recombinant IL-10 and PEGylated variants for chronic inflammatory diseases and oncology, although clinical application is often limited by systemic side effects such as anemia and thrombocytopenia.

Other names

Interleukin-10 regulatory cytokine pathwayIL-10/STAT3 signaling pathwayIL-10/JAK/STAT pathwayCytokine synthesis inhibitory factor pathway

Activation of the IL-10 receptor complex leads to JAK1/TYK2-mediated phosphorylation of STAT3, which translocates to the nucleus to regulate the transcription of anti-inflammatory genes and suppress pro-inflammatory cytokine production.