Interleukin-10-mediated anti-inflammatory pathway (IL-10 pathway)

The Interleukin-10 (IL-10)-mediated anti-inflammatory pathway is a fundamental regulatory mechanism of the immune system designed to resolve inflammation and maintain tissue homeostasis (Ouyang & O'Garra, 2019). Upon binding of the IL-10 cytokine to its cognate receptor complex (IL-10RA and IL-10RB), the Janus kinases JAK1 and TYK2 are activated, leading to the phosphorylation and nuclear translocation of the transcription factor STAT3 (Iyer & Cheng, 2012). Once in the nucleus, STAT3 drives the expression of genes that suppress the production of pro-inflammatory cytokines (e.g., TNF, IL-1, IL-6, IL-12) and induces feedback inhibitors like SOCS3 (Saraiva & O'Garra, 2010). This pathway is a major therapeutic target for chronic inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis, where IL-10 agonists like pegilodecakin are used to dampen overactive immune responses (Naing et al., 2018). Conversely, in the tumor microenvironment, the pathway can contribute to immune evasion, leading to the development of IL-10 or IL-10R inhibitors for cancer immunotherapy, although IL-10 can also paradoxically stimulate CD8+ T cells in certain oncology settings (Mumm et al., 2011). However, therapeutic modulation must be carefully managed due to risks of systemic immunosuppression and potential hematological side effects like anemia (Tilg et al., 2002).

Other names

IL-10 signaling pathwayIL-10/STAT3 signalingInterleukin-10 anti-inflammatory signaling

The pathway is activated by the binding of Interleukin-10 to its tetrameric receptor complex (IL-10RA/IL-10RB), leading to JAK1/TYK2-mediated phosphorylation of STAT3. Phosphorylated STAT3 homodimerizes and translocates to the nucleus to induce anti-inflammatory genes (e.g., SOCS3, SBNO2) and repress the transcription of pro-inflammatory cytokines (e.g., TNF-alpha, IL-6, IL-12).