IL-31 is expressed at low levels under normal physiological conditions, mainly produced by activated CD4+ Th2 cells, mast cells, monocytes/macrophages, and dendritic cells. The IL-31 functional receptor is a heterodimer complex composed of IL-31 receptor α (IL-31RA) and oncostatin M receptor (OSMR). The IL-31 receptor can be further divided into membrane-bound and soluble receptors, with membrane-bound receptors primarily found in activated monocytes, macrophages, myeloid progenitor cells, epidermal keratinocytes, eosinophils, epithelial cells, and lymphocytes, and are expressed at higher levels in skin and bronchial tissues.
IL-31, when binding to its receptors IL-31RA and OSMR in the extracellular domain, recruits and activates JAK1/2 kinases within the receptor cell. The JAK kinases activated by IL-31RA phosphorylate STAT1/3/5 signaling pathways, while those activated by OSMR can activate the PI3k/AKT signaling pathway and the ERK, P38, and JNK signaling pathways within the MAPK signaling pathway superfamily, leading to transcription of target genes and exerting various biological functions.
