AHR regulates the immunomodulatory function of human adipose-derived mesenchymal stem cells

Abstract

Objective To explore the effect of aryl hydrocarbon receptor(AHR) on the immunomodulatory function of human adipose derived mesenchymal stem cells (MSCs). Methods RT-qPCR and immunofluorescence staining were used to detect the expression levels of indoleamine 2,3-dioxygenase 1 (IDO1), interleukin-4-inducible gene 1 (IL4I1) and AHR in MSCs before and after inflammatory cytokine stimulation; siCtrl, siIDO1, siIL4I1 and siAHR were transfected into MSCs and blocked the AHR signaling pathway; conditioned medium from MSCs was co-incubated with macrophages, RT-qPCR and ELISA were performed to detect the level of IL-6, IL-1β, TNF-α. Results MSCs without cytokine stimulation highly expressed AHR and hardly expressed IDO1 and IL4I1 proteins; IDO1, IL4I1 and AHR were up-regulated after different cytokine stimulation(P＜0.05), the expression of IDO1 and IL4I1 was most significantly up-regulated after stimulation by IFN-γ(P＜0.001), AHR entering the nucleus was increased; down-regulation of AHR expression could inhibit the immunomodulatory effect of MSCs(P＜0.05). Conclusions AHR regulates the immune function of MSCs, downregulates expression of AHR could inhibit the immunomodulatory effects of MSCs.

Keywords

• aryl hydrocarbon receptor(ahr)|mesenchymal stem cells|immunomodulatory effects