IL-10 Signaling

Interleukin 10 (IL-10) is a cytokine with diverse, but mostly anti-inflammatory, effects on hematopoietic cells. It also regulates the growth and differentiation of B-cells, T-cells, NK-cells and dendritic cells.IL-10 binds IL-10Rα, the ligand binding chain of the tetrameric receptor. IL-10Rbeta serves to assemble the active receptor complexes and is shared with other IL-10 related cytokines. The binding of ligand to IL-10Rα induces a conformational change that enables IL-10Rβ to interact with the newly formed ligand-receptor complex. This in turn initiates a signal transduction cascade that activates TYK2 and JAK1 followed by STAT3. STAT3 homodimerizes and translocates into the nucleus. SOCS-3 (suppressor of cytokine signaling-3) inhibits JAK/STAT-dependent signaling, thus inhibiting pro-inflammatory genes like IL-1 and TNF-α.IL-1 binds to its cell surface receptor and initiates a signaling cascade via the adapter proteins TRAF6 and TAK1. TAK1 activates several downstream signaling pathways including the NIK/IKK/NF-κB, MKK4/JNK1 and MKK3/p38MAPK pathways. Activated NF-κB, JNK1 and p38MAPK translocate to the nucleus where, either directly or via transcriptional regulators like ELK-1, c-Jun and c-Fos, they induce genes that promote inflammation. (Upgraded 04/2022)