Interleukin-10

Definition:

Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3. In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators. Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro-inflammatory cytokines including granulocyte-macrophage colony-stimulating factor /GM-CSF, granulocyte colony-stimulating factor/G-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF-alpha. Interferes also with antigen presentation by reducing the expression of MHC-class II and co-stimulatory molecules, thereby inhibiting their ability to induce T cell activation. In addition, controls the inflammatory response of macrophages by reprogramming essential metabolic pathways including mTOR signaling (By similarity).

References:

[1]. F Willems, et al. Interleukin-10 inhibits B7 and intercellular adhesion molecule-1 expression on human monocytes. Eur J Immunol. 1994 Apr;24(4):1007-9. [Content Brief]

[2]. Sung Il Yoon, et al. Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex. J Biol Chem. 2006 Nov 17;281(46):35088-96. [Content Brief]

[3]. Karim C El Kasmi, et al. Cutting edge: A transcriptional repressor and corepressor induced by the STAT3-regulated anti-inflammatory signaling pathway. J Immunol. 2007 Dec 1;179(11):7215-9. [Content Brief]

[4]. R de Waal Malefyt, et al. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209-20. [Content Brief]

[5]. S I Hashimoto, et al. IL-10 inhibits granulocyte-macrophage colony-stimulating factor-dependent human monocyte survival at the early stage of the culture and inhibits the generation of macrophages. J Immunol. 2001 Oct 1;167(7):3619-25. [Content Brief]

[6]. K Frei, et al. Antigen presentation in the central nervous system. The inhibitory effect of IL-10 on MHC class II expression and production of cytokines depends on the inducing signals and the type of cell analyzed. J Immunol. 1994 Mar 15;152(6):2720-8. [Content Brief]

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