Vitamin D3 mitigates autoimmune inflammation caused by activation of myeloid dendritic cells in SLE

作者全名："Li, Mingfang; Luo, Li; Lin, Chuanchuan; Ni, Bing; Zou, Liyun; Song, Zhiqiang; Hao, Fei; Wu, Yi; Luo, Na"

作者地址："[Li, Mingfang; Luo, Li; Hao, Fei; Luo, Na] Chongqing Med Univ, Affiliated Hosp 3, Dept Dermatol, Chongqing, Peoples R China; [Li, Mingfang; Luo, Li; Lin, Chuanchuan; Song, Zhiqiang; Hao, Fei; Luo, Na] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Dept Dermatol, Chongqing, Peoples R China; [Li, Mingfang] Guangzhou Med Univ, Affiliated Hosp 3, Dept Dermatol, Guangzhou, Peoples R China; [Ni, Bing; Zou, Liyun] Third Mil Med Univ, Army Med Univ, Inst Immunol, Chongqing, Peoples R China; [Wu, Yi] Third Mil Med Univ, Army Med Univ, Coll Biomed Engn & Med Imaging, Dept Digital Med, Chongqing, Peoples R China; [Luo, Na] Chongqing Med Univ, Affiliated Hosp 3, Dept Dermatol, 1 Shuanghu Rd, Chongqing 401120, Peoples R China"

通信作者："Luo, N (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Dermatol, 1 Shuanghu Rd, Chongqing 401120, Peoples R China."

来源：EXPERIMENTAL DERMATOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001066244500001

JCR分区：Q1

影响因子：3.5

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词："1,25(OH)2D3; autoimmune inflammation; DNA-containing immune complexes; myeloid; dendritic cells; systemic lupus erythematosus; Treg/Th17 immune balance"

摘要："Systemic lupus erythematosus (SLE) is an autoimmune disease in which defective T cells, immune complex deposition and other immune system alterations contribute to pathological changes of multiple organ systems. The vitamin D metabolite c is a critical immunomodulator playing pivotal roles in the immune system. Epidemiological evidence indicates that vitamin D deficiency is correlated with the severity of SLE. Our aim is to investigate the effects of 1,25(OH)2D3 (VitD3) on the activation of myeloid dendritic cells (mDCs) by autologous DNA-containing immune complex (DNA-ICs), and the effects of VitD3 on immune system balance during SLE. We purified DNA-ICs from the serum of SLE patients and isolated mDCs from normal subjects. In vitro studies showed that DNA-ICs were internalized and consumed by mDCs. VitD3 blocked the effects of DNA-ICs on RelB, IL-10 and TNF-alpha in mDCs. Further analysis indicated that DNA- ICs stimulated histone acetylation in the RelB promoter region, which was inhibited by VitD3. Knockdown of the histone deacetylase 3 gene (HDAC3) blocked these VitD3-mediated effects. Co-culture of mDCs and CD4(+) T cells showed that VitD3 inhibited multiple processes mediated by DNA-ICs, including proliferation, downregulation of IL-10, TGF-ss and upregulation of TNF-alpha. Moreover, VitD3 could also reverse the effects of DNA-IC- induced imbalance of CD4(+) CD127- Foxp3(+) T cells and CD4(+) IL17(+) T cells. Taken together, our results indicated that autologous DNA-ICs stimulate the activation of mDCs in the pathogenesis of SLE, and VitD3 inhibits this stimulatory effects of DNA-ICs by negative transcriptional regulation of RelB gene and maintaining the Treg/Th17 immune cell balance. These results suggest that vitamin D may have therapeutic value for the treatment of SLE."

基金机构："Chongqing Excellence Program [cstc2021ycjh-bgzxm0291]; National Natural Science Foundation of China [81000696, 81472884]; Funding for Key Disciplines of Third Affiliated Hospital of Chongqing Medical University [ZK201902]"

基金资助正文："Chongqing Excellence Program, Grant/Award Number: cstc2021ycjh-bgzxm0291; National Natural Science Foundation of China, Grant/Award Number: 81000696 and 81472884; the Funding for Key Disciplines of Third Affiliated Hospital of Chongqing Medical University, Grant/Award Number: ZK201902"