Dll4 in the DCs isolated from OVA-sensitized mice is involved in Th17 differentiation inhibition by 1,25-dihydroxyvitamin D3 in vitro.
BACKGROUND
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.
a Institute of Human Respiratory Disease, Xinqiao Hospital, Third Military Medical University , Chongqing , China.
Yunqiu
Y
Jiang
a Institute of Human Respiratory Disease, Xinqiao Hospital, Third Military Medical University , Chongqing , China.
Shengtao
S
Zhao
a Institute of Human Respiratory Disease, Xinqiao Hospital, Third Military Medical University , Chongqing , China.
Xu
X
Yang
a Institute of Human Respiratory Disease, Xinqiao Hospital, Third Military Medical University , Chongqing , China.
Yu
Y
Liu
a Institute of Human Respiratory Disease, Xinqiao Hospital, Third Military Medical University , Chongqing , China.
Changzheng
C
Wang
D000818:Animals; D001249:Asthma; D002117:Calcitriol / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism*
C098680:Il17a protein, mouse; D020381:Interleukin-17; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C064045:delta protein; D003907:Dexamethasone; D010047:Ovalbumin; D002117:Calcitriol
1,25-dihydroxyvitamin D3; T helper 17 cell; asthma treatment; delta-like ligand 4; dendritic cells