IL10

IL-10 (Interleukin-10, also known as Cytokine Synthesis Inhibitory Factor/CSIF) is the prototypical anti-inflammatory cytokine and founding member of the IL-10 family. It is a secreted homodimeric four-helix-bundle cytokine (~36 kDa dimer) that signals through a heterotetrameric receptor complex comprising two IL-10RA (ligand-binding) and two IL-10RB (signal-transducing) chains. Receptor engagement activates JAK1 (via IL-10RA) and TYK2 (via IL-10RB), leading to STAT3 phosphorylation, dimerization, nuclear translocation, and transcription of anti-inflammatory target genes (e.g., SOCS3, IL1RN). IL-10 is produced by multiple immune cell types including monocytes/macrophages, dendritic cells, T cell subsets (Th1, Th2, Treg), B cells, and NK cells. Its principal function is to suppress inflammatory responses by inhibiting pro-inflammatory cytokine production (TNF, IL-1, IL-6, IL-8, IL-12) in monocytes/macrophages, downregulating MHC class II expression and co-stimulatory molecules, and limiting T cell activation. IL-10 also has immunostimulatory effects on B cells (promoting proliferation, differentiation, and immunoglobulin production) and CD8+ T cells in certain contexts. Loss-of-function mutations in IL10 or IL10R cause very-early-onset inflammatory bowel disease (VEO-IBD), establishing IL-10 signaling as essential for intestinal immune homeostasis.

Disorders

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