T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow.
T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow.
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DOI：
10.1016/j.celrep.2017.01.067
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发表时间：
2017-02-21
期刊：
影响因子：
8.8
通讯作者：
Hunter CA
中科院分区：
文献类型：
--
作者：
Glatman Zaretsky A;Konradt C;Dépis F;Wing JB;Goenka R;Atria DG;Silver JS;Cho S;Wolf AI;Quinn WJ;Engiles JB;Brown DC;Beiting D;Erikson J;Allman D;Cancro MP;Sakaguchi S;Lu LF;Benoist CO;Hunter CA
骨髓(BM)中的长寿命浆细胞(PC)是感染或接种后产生抗体的关键来源，但控制PC的因素仍然存在疑问。我们发现，系统性感染改变了骨髓，极大地减少了PC和调节性T(Treg)细胞，这是一个有助于骨髓免疫豁免的群体。活体成像的使用表明，BM Treg细胞表现出独特的行为，其特征是与PC和CD11c-YFP+细胞持续共存。基因表达谱显示，BM Treg细胞表达高水平的Treg效应分子，这些细胞中CTLA-4的缺失导致PC升高。此外，在系统感染期间保存Treg细胞可以防止PC丢失，而在未感染的小鼠中Treg细胞枯竭会减少PC数量。这些研究提示了Treg细胞在PC生物学中的作用，并为疫苗诱导的体液反应或自身免疫期间PC的调节提供了一个潜在的靶点。
Long-lived plasma cells (PC) in the bone marrow (BM) are a critical source of antibodies after infection or vaccination, but questions remain about the factors that control PCs. We found that systemic infection alters the BM, greatly reducing PCs and regulatory T (Treg) cells, a population that contributes to immune privilege in the BM. The use of intravital imaging revealed that BM Treg cells display a distinct behavior characterized by sustained co-localization with PCs and CD11c-YFP+ cells. Gene expression profiling indicated that BM Treg cells express high levels of Treg effector molecules, and CTLA-4 deletion in these cells resulted in elevated PCs. Furthermore, preservation of Treg cells during systemic infection prevents PC loss, while Treg cell depletion in uninfected mice reduced PC populations. These studies suggest a role for Treg cells in PC biology and provide a potential target for the modulation of PCs during vaccine-induced humoral responses or autoimmunity.