Dll4 in the DCs isolated from OVA-sensitized mice is involved in Th17 differentiation inhibition by 1,25-dihydroxyvitamin D3 in vitro

Introduction:T helper 17 cell (Th17) cells play an important role in neutrophilic asthma, and 1,25(OH)2D3 has been reported to modulate the proliferation and differentiation of T cells. In this study, we examined the effects of 1,25(OH)2D3 on the dendritic cell (DC)-mediated regulation of Th17differentiation from OVA-sensitized mice.

Methods:DCs were isolated from ovalbumin-sensitized mouse spleens. Lipopolysaccharide (LPS) was administered to stimulate the DCs for 24 h, and dexamethasone or 1,25(OH)2D3 was applied simultaneously. The expression of Notch ligand delta-like ligand 4 (Dll4) in the DCs was detected in each group. All the groups of treated DCs were co-cultured with T cells, and Dll4 was inhibited in these groups. After 24 h, Th17 and Treg cell differentiation and the IL-17A levels were measured.

Results:Dll4 expression was increased in LPS-treated DCs compared with the control group (p = 0.05), resulting in increased Th17 cell differentiation (p = 0.002). Treatment with 1,25(OH)2D3 inhibited the Dll4 expression(p = 0.04) and decreased Th17 cell differentiation (p = 0.001) in DCs that was induced by LPS. Directly inhibiting Dll4 reduced Th17 cell differentiation, and Th17 cell differentiation was not further inhibited by 1,25(OH)2D3 once Dll4 was blocked.

Conclusions:These result suggest that Dll4 in the DCs isolated from OVA-sensitized mice is involved in Th17 differentiation inhibition by 1,25(OH)2D3.

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