Involvement of suppressive B-lymphocytes in the mechanism of tolerogenic dendritic cell reversal of type 1 diabetes in NOD mice.

Involvement of suppressive B-lymphocytes in the mechanism of tolerogenic dendritic cell reversal of type 1 diabetes in NOD mice.
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DOI:
10.1371/journal.pone.0083575
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Giannoukakis N
Giannoukakis N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Di Caro V;Phillips B;Engman C;Harnaha J;Trucco M;Giannoukakis N

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这项研究的目的是确定除Foxp3+T调节细胞外的免疫细胞群体,这些细胞参与非肥胖糖尿病(NOD)小鼠品系中耐受性树突状细胞预防和逆转1型糖尿病的作用机制。与NOD耐受树突状细胞和B细胞以及转基因IL-10启动子报告基因小鼠的共培养实验以及将耐受树突状细胞和CD19+B细胞转移到NOD和转基因小鼠中的实验表明,这些树突状细胞在体外和体内都能增加表达IL-10的B细胞的频率和数量。这些细胞的扩增既是先前存在的表达IL-10的B淋巴细胞增殖的结果,也是CD19+B淋巴细胞转化为表达IL-10的细胞的结果。致耐受树突状细胞不影响这些B细胞的抑制活性。此外,我们还发现,抑制的小鼠B淋巴细胞表达由耐受性树突状细胞产生的维甲酸受体。这些数据有助于确定临床试验中耐受树突状细胞反应增加的B细胞群体的性质,也验证了最新的发现,证明了人类耐受树突状细胞和免疫抑制调节性B细胞之间存在机制联系。
The objective of the study was to identify immune cell populations, in addition to Foxp3+ T-regulatory cells, that participate in the mechanisms of action of tolerogenic dendritic cells shown to prevent and reverse type 1 diabetes in the Non-Obese Diabetic (NOD) mouse strain. Co-culture experiments using tolerogenic dendritic cells and B-cells from NOD as well as transgenic interleukin-10 promoter-reporter mice along with transfer of tolerogenic dendritic cells and CD19+ B-cells into NOD and transgenic mice, showed that these dendritic cells increased the frequency and numbers of interleukin-10-expressing B-cells in vitro and in vivo. The expansion of these cells was a consequence of both the proliferation of pre-existing interleukin-10-expressing B-lymphocytes and the conversion of CD19+ B-lymphcytes into interleukin-10-expressing cells. The tolerogenic dendritic cells did not affect the suppressive activity of these B-cells. Furthermore, we discovered that the suppressive murine B-lymphocytes expressed receptors for retinoic acid which is produced by the tolerogenic dendritic cells. These data assist in identifying the nature of the B-cell population increased in response to the tolerogenic dendritic cells in a clinical trial and also validate very recent findings demonstrating a mechanistic link between human tolerogenic dendritic cells and immunosuppressive regulatory B-cells.
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