IL-10R alpha

IL-10R alpha is a ligand-binding subunit of the type II cytokine receptor consisting of 2 alpha and 2 beta subunits and is expressed primarily in hematopoietic cells such as B cells, T cells, NK cells, monocytes and macrophages, but not in non-hematopoietic cells such as fibroblasts or endothelial cells. IL-10R alpha binds to the ligand and leads to a conformational change in the beta subunit, which results in the beta subunit also binding IL-10, forming a heterotetramer that leads to activation of the signalling complex of JAK1 and TYK2 kinases. In this case, JAK1 binds to the alpha subunit and TYK2 binds to the beta subunit, phosphorylating specific tyrosine residues in the intracellular structural domain of IL10R alpha. This further leads to phosphorylation and activation of the transcription factor STAT3, which dimerises STAT3 monomers into the nucleus and induces transcriptional expression of the target gene^[1]. IL-10R alpha is involved in suppressing inflammatory responses and Th 1 cell-mediated immune responses, and also regulates neutrophil functional responses. In addition, IL10R alpha-mediated activation of STAT3 also inhibits starvation-induced autophagy^[2].

References: