Effects of 1α, 25-dihydroxyvitamin D3 on memory CD4+ T cells of focal proliferative IgA nephropathy
10.3760/cma.j.issn.1001-7097.2014.07.002
- VernacularTitle:骨化三醇对局灶增生性IgA肾病患者CD4+记忆性T细胞的影响
- Author:
Chunyang YU
;
Jing LUO
;
Rongshan LI
;
Lihua WANG
;
Hui GUO
- Publication Type:Journal Article
- Keywords:
1 alpha,25 Dihydroxyvitamin D3;
Glomerulonephraritis,IgA;
CD4+ T-lymphocytes;
Proteinuria
- From:
Chinese Journal of Nephrology
2014;30(7):486-493
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on memory CD4+T cells of focal proliferative IgA nephropathy (IgAN)patients.Methods (1) Total of twenty incipient focal proliferative IgAN patients (Lee classification:Ⅲ level) were chosen as IgAN group and 20 healthy volunteers were chosen as healthy control group.The level of serum 1,25(OH)2D3 was measured by radioimmunoassay (RIA).Peripheral blood mononuclear cells (PBMCs) were separated by the method of Ficoll density gradient centrifugation and were stimulated with anti-CD3/anti-CD28 in the absence or presence of various concentrations of 1,25(OH)2D3,Dexamethasone(DEX) and 1,25(OH)2D3and DEX combined.PBMCs were cultured for 72 hours and the levels of IFN-γ,IL-4,IL-17A,Foxp3 were measured by flow cytometry(FCM),standing for the levels of Th1,Th2,Th17,Treg.(2) IgAN group was divided into two subgroups (proteinuria ＜ 1 g/24 h subgroup,proteinuria≥ 1 g/24 h subgroup),then the serum levels of 1,25(OH)2D3,IFN-γ,IL-4,IL-17A,Foxp3 were compared.Results Compared with healthy control group,serum 1,25(OH)2D3 level of IgAN group was significantly lower (P ＜ 0.05).Serum 1,25(OH)2D3 level in proteinuria≥ 1 g/24 h subgroup was significantly lower than proteinuria ＜ 1 g/24 h subgroup and healthy control group (P ＜ 0.05).The level in proteinuria ＜ 1 g/24 h subgroup was lower than healthy control group,but the difference was not statistically significant (P ＞ 0.05).(2) The levels of IFN-γ and IL-17A and the ratios of IFN-γ/IL-4,IL-17A/Foxp3 in IgAN group increased significantly compared with healthy control group (all P ＜ 0.05),and the level of Foxp3 decreased significantly (P ＜ 0.05).The level of IL-4 also increased,but the difference was not statistically significant (P ＞ 0.05).The levels of IFN-γand IL-17A and the ratio of IL-17A/Foxp3 in proteinuria≥ 1 g/24 h subgroup increased significantly,and the level of Foxp3 decreased significantly,compared with urinary protein ＜ 1 g/24 h subgroup and healthy control group (P ＜ 0.05).The ratio of IFN-γ/IL-4 in proteinuria≥1 g/24 h subgroup and proteinuria ＜ 1 g/24 h subgroup all increased,compared with healthy control group,and the ratio in proteinuria≥ 1 g/24 h subgroup increased significantly (P ＜ 0.05).There was no significant difference in the level of IL-4 among all groups.(3) After treatment with 1,25(OH)2D3,the levels of IFN-γ and IL-17A and the ratios of IFN-γ/IL-4 and IL-17A/Foxp3 decreased significantly,and the level of Foxp3 increased significantly (P ＜ 0.05),and these effects were more obvious as the increase of the drug concentration.The level of IL-4 did not change significantly.The combination of 1,25(OH)2D3 and DEX had a synergistic inhibition on the production of IFN-γ,IL-4,IL-17A,and the ratios of IFN-γ/IL-4 and IL-17A/Foxp3,and had a synergistic promotion on the production of Foxp3.Conclusions There is a certain extent of vitamin D deficiency in focal proliferative IgAN patients,which may be associated with the severity of proteinuria.The disorder of immunomodulatory effects of memory CD4+ T cell might exist in the patients of focal proliferative IgAN.1α,25-dihydroxyvitamin D3 might have beneficial effects on the immunoregulation of memory CD4+T cells of focal proliferative IgAN patients.
