D-mannose ameliorates autoimmune phenotypes in mouse models of lupus.
D-mannose ameliorates autoimmune phenotypes in mouse models of lupus.
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DOI：
10.1186/s12865-020-00392-7
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发表时间：
2021-01-05
期刊：
影响因子：
3
通讯作者：
Morel L
中科院分区：
文献类型：
--
作者：
Wang H;Teng X;Abboud G;Li W;Ye S;Morel L
系统性红斑狼疮是一种自身免疫性疾病，其特征是多种免疫细胞类型的失调导致自身抗体的过度产生。D-甘露糖是葡萄糖的C-− -2异构体，在自身免疫性疾病的模型中表现出免疫调节作用，如1型糖尿病、诱导性类风湿性关节炎和呼吸道炎症。本研究旨在评价D-甘露糖对狼疮小鼠模型的治疗效果。首先，用流式细胞术检测D-甘露糖对非自身免疫性C57BL/6(B6)小鼠骨髓来源的树突状细胞(BMDCs)体外活化及其诱导抗原特异性CD4+T细胞增殖和活化的影响。D-甘露糖抑制BMDCs的成熟及其诱导抗原特异性T细胞的增殖和激活。在体内，D-甘露糖增加了未经处理的B6小鼠中Foxp3+调节性T细胞的频率。为了评估D-甘露糖在狼疮小鼠模型中的作用，我们使用了移植物抗宿主病(CGVHD)诱导的模型和B6.lpr自发模型。在cGVHD模型中，D-甘露糖治疗减少了自身抗体的产生，伴随着效应器记忆和毛囊辅助T细胞以及生发中心B细胞和浆细胞的频率降低。这些结果在自发性狼疮的B6.lpr模型中得到了部分验证。总体而言，我们的结果表明，D-甘露糖改善了狼疮模型中的自身免疫激活，至少部分是由于它扩增了Treg细胞，诱导了未成熟的常规树突状细胞，并下调了效应器T细胞的激活。然而，与其他自身免疫性疾病相比，D-甘露糖在狼疮中的免疫调节作用较弱。网上版载有补充材料，可在10.1186/s12865-020-00392-7查阅。
Systemic lupus erythematosus is an autoimmune disease characterized by an overproduction of autoantibodies resulting from dysregulation in multiple immune cell types. D-mannose is a C− 2 epimer of glucose that exhibits immunoregulatory effects in models of autoimmune diseases, such as type 1 diabetes, induced rheumatoid arthritis, and airway inflammation. This study was conducted to evaluate the efficacy of D-mannose treatment in mouse models of lupus. Firstly, the effect of D-Mannose was evaluated by flow cytometry on the in vitro activation of non-autoimmune C57BL/6 (B6) bone marrow-derived dendritic cells (BMDCs) and their ability to induce antigen-specific CD4+ T cell proliferation and activation. D-mannose inhibited the maturation of BMDCs and their induction of antigen-specific T cell proliferation and activation. In vivo, D-mannose increased the frequency of Foxp3+ regulatory T cells in unmanipulated B6 mice. To assess the effect of D-mannose in mouse models of lupus, we used the graft-versus-host disease (cGVHD) induced model and the B6.lpr spontaneous model. In the cGVHD model, D-mannose treatment decreased autoantibody production, with a concomitant reduction of the frequency of effector memory and follicular helper T cells as well as germinal center B cells and plasma cells. These results were partially validated in the B6.lpr model of spontaneous lupus. Overall, our results suggest that D-mannose ameliorates autoimmune activation in models of lupus, at least partially due to its expansion of Treg cells, the induction of immature conventional dendritic cells and the downregulation of effector T cells activation. D-Mannose showed however a weaker immunomodulatory effect in lupus than in other autoimmune diseases. The online version contains supplementary material available at 10.1186/s12865-020-00392-7.
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影响因子：
7.3
作者：
Yang F;Fan X;Huang H;Dang Q;Lei H;Li Y
通讯作者：
Li Y
影响因子：
16.6
作者：
Choi SC;Titov AA;Abboud G;Seay HR;Brusko TM;Roopenian DC;Salek-Ardakani S;Morel L
通讯作者：
Morel L
影响因子：
5
作者：
Cuda, C. M.;Zeumer, L.;Sobel, E. S.;Croker, B. P.;Morel, L.
通讯作者：
Morel, L.
CD163+ M2C样巨噬细胞在狼疮肾炎患者的肾脏活检中占主导地位。
影响因子：
4.9
作者：
Olmes G;Büttner-Herold M;Ferrazzi F;Distel L;Amann K;Daniel C
通讯作者：
Daniel C
DOI：
10.4049/jimmunol.1601565
发表时间：
2017-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Sung SJ;Ge Y;Dai C;Wang H;Fu SM;Sharma R;Hahn YS;Yu J;Le TH;Okusa MD;Bolton WK;Lawler JR
通讯作者：
Lawler JR