JAK/STAT3 signaling pathway mediates endothelial-like differentiation of immature dendritic cells

Abstract

Endothelial-like differentiation (ELD) of dendritic cells (DCs) is a poorly understood phenomenon. The present study evaluated the effect on the ELD of DCs by using human esophageal squamous cell carcinoma (ESCC) cells with high or poor differentiation. The results demonstrated that KYSE450 (highly differentiated) and KYSE70 (poorly differentiated) cell supernatants induce the differentiation of immature DCs (iDCs), derived from healthy adult volunteers, away from the DC pathway and towards an endothelial cell (EC) fate. This effect was strongest in the cells treated with the KYSE70 supernatant. During the ELD of iDCs, sustained activation of JAK (janus tyrosine kinase)/STAT3 (signal transducer and activator of transcription 3) signaling was detected. Incubation of iDCs with the JAK inhibitor, AG490 blocked JAK/STAT3 phosphorylation and iDC differentiation. These results suggested that the JAK/STAT3 signaling pathway mediates ELD of iDCs. Furthermore, the poorly differentiated ESCC cells may have a greater effect on the ELD of iDCs than highly differentiated ESCC cells.