Myeloid-derived suppressor cells prevent type 1 diabetes in murine models.
Myeloid-derived suppressor cells prevent type 1 diabetes in murine models.
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髓样衍生的抑制细胞可预防鼠模型中1型糖尿病。
DOI：
10.4049/jimmunol.0903636
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发表时间：
2010-11-15
期刊：
影响因子：
--
通讯作者：
Pan PY
中科院分区：
文献类型：
--
作者：
Yin B;Ma G;Yen CY;Zhou Z;Wang GX;Divino CM;Casares S;Chen SH;Yang WC;Pan PY
1型糖尿病（T1D）的有效免疫治疗依赖于积极诱导外周耐受。髓源性抑制细胞（MDSCs）通过多种机制，包括调节性T细胞（Tregs）的扩增，在多种病理环境下抑制免疫反应中发挥关键作用。在这项研究中，我们研究了MDSCs是否可以作为apc诱导ag特异性treg扩增，抑制T细胞增殖，并防止自身免疫性T1D的发展。我们发现mdsc介导的treg扩增和T细胞抑制需要mhc依赖性Ag呈递。在INS-HA/RAG - / -小鼠中建立小鼠T1D模型，动物通过过继性转移接受CD4-HA-TCR转基因T细胞。我们发现，在接受MDSC + HA治疗的小鼠中，糖尿病的发病率显著降低，而接受OVA肽治疗的小鼠中，75%的小鼠无糖尿病。为了进一步测试MDSCs是否可以预防NOD小鼠的糖尿病发作，将来自糖尿病NOD小鼠的炎症T细胞注射给非糖尿病NOD/SCID小鼠。MDSCs显著地预防了糖尿病的发生，60%的MDSCs处理的小鼠保持无糖尿病状态。与对照组相比，治疗组小鼠胰岛淋巴细胞浸润水平明显降低，胰岛素炎发生率明显降低。MDSCs的保护作用可能是通过诱导自身反应性T细胞的能量和CD4+CD25+Foxp3+ Tregs的发育来介导的。这项研究表明，转移的MDSCs具有显著的下调ag特异性自身免疫反应和预防糖尿病发病的能力，这表明MDSCs在控制T1D和其他自身免疫性疾病方面具有巨大的潜力，是一种新的基于细胞的耐受性治疗方法。
Effective immunotherapy for type 1 diabetes (T1D) relies on active induction of peripheral tolerance. Myeloid-derived suppressor cells (MDSCs) play a critical role in suppressing immune responses in various pathologic settings via multiple mechanisms, including expansion of regulatory T cells (Tregs). In this study, we investigated whether MDSCs could act as APCs to induce expansion of Ag-specific Tregs, suppress T cell proliferation, and prevent autoimmune T1D development. We found that MDSC-mediated expansion of Tregs and T cell suppression required MHC-dependent Ag presentation. A murine T1D model was established in INS-HA/RAG−/− mice in which animals received CD4-HA-TCR transgenic T cells via adoptive transfer. We found a significant reduction in the incidence of diabetes in recipients receiving MDSC plus HA, but not OVA peptide, leading to 75% diabetes-free mice among the treated animals. To test further whether MDSCs could prevent diabetes onset in NOD mice, nondiabetic NOD/SCID mice were injected with inflammatory T cells from diabetic NOD mice. MDSCs significantly prevented diabetes onset, and 60% of MDSC-treated mice remained diabetes free. The pancreata of treated mice showed significantly lower levels of lymphocyte infiltration in islet and less insulitis compared with that of the control groups. The protective effects of MDSCs might be mediated by inducing anergy in autoreactive T cells and the development of CD4+CD25+Foxp3+ Tregs. Thist study demonstrates a remarkable capacity of transferred MDSCs to downregulate Ag-specific autoimmune responses and prevent diabetes onset, suggesting that MDSCs possess great potential as a novel cell-based tolerogenic therapy in the control of T1D and other autoimmune diseases.
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影响因子：
6.2
作者：
Zhang W;Liang S;Wu J;Horuzsko A
通讯作者：
Horuzsko A
影响因子：
32.4
作者：
Sarukhan, A;Garcia, C;von Boehmer, H
通讯作者：
von Boehmer, H
DOI：
10.1084/jem.193.11.1327
发表时间：
2001-06-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Wu Q;Salomon B;Chen M;Wang Y;Hoffman LM;Bluestone JA;Fu YX
通讯作者：
Fu YX
影响因子：
11.2
作者：
Zea, AH;Rodriguez, PC;Ochoa, AC
通讯作者：
Ochoa, AC
影响因子：
82.9
作者：
Belghith, M;Bluestone, JA;Chatenoud, L
通讯作者：
Chatenoud, L