Effect of 1,25-dihydroxyvitamin D3 on Th17 and Th1 response in patients with Behçet's disease.
OBJECTIVE
1,25-Dihydroxyvitamin D3 (VitD3) has been shown to have immunoregulatory properties in animal models. In this study, we investigated its inhibitory effect on the immune response in Behçet's disease (BD) patients and the possible mechanisms involved.


METHODS
Naive CD4(+) T cells from active BD patients and normal controls were cultured under Th17 polarizing conditions in the presence or absence of VitD3, and cytokine production was determined by ELISA and flow cytometry. mRNA expression of several factors related to Th17 cell function was determined by real-time PCR. RNA interference for IFN regulatory factor 8 (IRF-8) was performed to study whether it was involved in the inhibitory effect of VitD3 on Th17 cell differentiation. The effect of VitD3-treated dendritic cells (DCs) on CD4(+) T cell response was determined by ELISA and flow cytometry.


RESULTS
Stimulation of naive CD4(+) T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in active BD patients. The addition of VitD3 significantly inhibited Th17 cell differentiation both in BD patients and in normal controls. The knockdown of IRF-8 by RNA interference significantly decreased the suppressive effect of VitD3 on Th17 differentiation. VitD3 was able to inhibit the gene expression of RORC, IL-17, IL-23R, CCR6, and Th1 cell differentiation, but upregulated IL-10 expression. VitD3-treated DCs significantly inhibited the Th17 and Th1 response.


CONCLUSIONS
The findings suggest that the inhibitory effect of VitD3 on the Th17 and Th1 response was mediated via both T cells and DCs and that the IRF-8 pathway is involved in the direct inhibition of VitD3 on Th17 cell differentiation.
First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, People's Republic of China.
Yuan
Y
Tian
Chaokui
C
Wang
Zi
Z
Ye
Xiang
X
Xiao
Aize
A
Kijlstra
Peizeng
P
Yang
D000328:Adult; D001528:Behcet Syndrome / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D034741:RNA, Small Interfering / Q000235:genetics; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology*; D000099185:Interferon Regulatory Factor-8
D002117:Calcitriol; D050835:Interferon Regulatory Factors; D007371:Interferon-gamma; D016753:Interleukin-10; D020381:Interleukin-17; D034741:RNA, Small Interfering; D014815:Vitamins; D000099185:Interferon Regulatory Factor-8; C508609:IL10 protein, human; C508717:IL17A protein, human