T helper 2 cells(Th2) and group 2 innate lymphoid cells (ILC2s) were reported to serve a critical role in allergic inflammation development by producing large amounts of IL-5 and IL-13 under allergen. Mesenchymal stem cells were reported to suppress Th2 and ease allergy inflammation. However, whether MSC negatively modulated ILC2 is unknown.
Human PBMC or ILC2 were isolated and stimulated with IL2/25/33. The effect of iPSC-MSCs on ILC2 in co-culture with or without transwell or by intravenous injection of iPSC-MSCs to IL-33 induced mice model. IL-5 and IL-13 expression were examined in protein and mRNA level. PDL1 and PDL2 expression in iPSC-MSCs were examined using flow cytometry.
PBMCs from allergic rhinitis and asthma patients were more sensitive to epithelium-derived cytokines than health group. In co-culture, human induced pluripotent stem cells (iPSCs)-derived MSCs (iPSC-MSCs) significantly reduced IL2/25/33 induced IL-5 and IL-13 production by ILC2, which was reversed by transwell separation. iPSC-MSCs expressed higher PDL1 and PDL2 than control. Both PDL2 and PDL1 reduced IL2/25/33 induced IL-5 and IL13 expression in ILC2; however, PDL2 showed a stronger suppressive effect than PDL1. In IL-33 induced allergy inflammation mice model, MSC reduced IL-13 expression in bronchoalveolar lavage fluid and the score of PAS staining.
Human iPSC-MSCs showed a suppressive effect on ILC2, which was dependent of cell-to-cell contact. These effect may be caused by PDL1 and PDL2.