Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues.
Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues.
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DOI：
10.4049/jimmunol.0803543
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发表时间：
2009-03-01
期刊：
影响因子：
--
通讯作者：
Tang Q
中科院分区：
文献类型：
--
作者：
Melli K;Friedman RS;Martin AE;Finger EB;Miao G;Szot GL;Krummel MF;Tang Q
树突状细胞（Dendritic cells，DC）在1型糖尿病胰岛中T细胞介导的胰岛素产生β细胞的破坏中是必不可少的。在这项研究中，我们研究了在自身免疫易感NOD和耐药C57 BL/6小鼠的疾病进展过程中，T细胞诱导胰岛内DC成熟。我们证明了两种小鼠品系中半成熟胰岛内DC对未加工的β细胞衍生蛋白的稳态捕获和保留。T细胞介导的胰岛内炎症诱导了CD 40和CD 80表达的增加，以及驻留DC对捕获的Ag的加工，而不诱导IL-12/23的p40亚基的表达。在急性胰岛内炎症小鼠的胰腺淋巴结中检测到一些CD 40 high胰岛内DC上调CCR 7，并且少量携带未处理的胰岛Ag的CD 40 high DC，表明T细胞介导的组织炎症增加了成熟驻留DC向引流淋巴结的迁移。我们的研究结果确定了自身免疫性糖尿病进展过程中的一个放大环，其中初始T细胞浸润导致胰岛内DC快速成熟，它们迁移到淋巴结，并扩大引发更多的自身反应性T细胞。阻断这一过程的治疗干预可能有效地阻止1型糖尿病的进展。
Dendritic cells (DCs) are essential in T cell-mediated destruction of insulin-producing β cells in the islets of Langerhans in type 1 diabetes. In this study, we investigated T cell induction of intra-islet DC maturation during the progression of the disease in both autoimmune-prone NOD and resistant C57BL/6 mice. We demonstrated steady-state capture and retention of unprocessed β cell-derived proteins by semimature intra-islet DCs in both mouse strains. T cell-mediated intra-islet inflammation induced an increase in CD40 and CD80 expression and processing of captured Ag by resident DCs without inducing the expression of the p40 subunit of IL-12/23. Some of the CD40high intra-islet DCs up-regulated CCR7, and a small number of CD40high DCs bearing unprocessed islet Ags were detected in the pancreatic lymph nodes in mice with acute intra-islet inflammation, demonstrating that T cell-mediated tissue inflammation augments migration of mature resident DCs to draining lymph nodes. Our results identify an amplification loop during the progression of autoimmune diabetes, in which initial T cell infiltration leads to rapid maturation of intra-islet DCs, their migration to lymph nodes, and expanded priming of more autoreactive T cells. Therapeutic interventions that intercept this process may be effective at halting the progression of type 1 diabetes.
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DOI：
10.1084/jem.20061577
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fife BT;Guleria I;Gubbels Bupp M;Eagar TN;Tang Q;Bour-Jordan H;Yagita H;Azuma M;Sayegh MH;Bluestone JA
通讯作者：
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DOI：
10.1084/jem.186.12.2057
发表时间：
1997-12-15
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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Miller JF
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
4.4
作者：
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通讯作者：
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