IL-22 and Its Receptors, New Players in the Inflammatory Network

Laure      Dumoutier; Jean-Christophe      Renauld

Abstract

Originally identified as a gene specifically induced by IL-9 in a mouse T cell lymphoma, IL-22 is mainly produced by TH1 cells or by activated T cells. Human IL-22, which shares 79% amino acid identity with its mouse orthologue and 25% with IL-10 is encoded by a single copy gene and located on chromosome 12, close to the IFNγ gene, whereas the murine IL-22 gene is located on chromosome 10 and is duplicated in some mouse strains. Structurally, IL-22 appears to be a monomer composed of six alpha helices, whose organization is reminiscent of the helices of the IL-10 dimer. Despite its structural relationship with IL-10, IL-22 exerts completely different activities, acting mainly on non hematopoietic cells, such as epithelial cells from lung and colon, hepatocytes and keratinocytes. IL-22 might therefore be involved in inflammatory processes, at least in liver and skin. IL-22 exerts its activity via a complex formed by IL-10Rβ and IL-22R, associated with Tyk2 and Jak1, respectively. The main signaling pathways triggered by IL-22 involve STAT-1, - 3, -5 and the ERK, JNK and p38 MAPKinases. Beside its transmembrane receptor, IL-22 also binds to a soluble receptor, called IL-22BP. This soluble receptor turns out to be a natural antagonist of IL-22 biological activities at least in vitro.

Keywords: IL-22, inflammation, receptors

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