TLR2 signaling improves immunoregulation to prevent type 1 diabetes.
TLR2 signaling improves immunoregulation to prevent type 1 diabetes.
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TLR2信号传导可改善免疫调节以防止1型糖尿病。
DOI：
10.1002/eji.200939841
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发表时间：
2011-05
影响因子：
5.4
通讯作者：
von Herrath, Matthias G.
中科院分区：
文献类型：
--
作者：
Filippi, Christophe M.;Ehrhardt, Katrin;Estes, Elizabeth A.;Larsson, Par;Oldham, Janine E.;von Herrath, Matthias G.
通过Toll样受体2（TLR 2）的信号传导促进炎症并调节CD 4 + CD 25+调节性T细胞（TCR 4）。我们从机制上评估了这种分子如何改变1型糖尿病（T1 D）的免疫调节。我们还询问了TLR 2是否可能参与我们最近的发现，即病毒感染可以通过扩大和增强调节性T细胞（TCLs）来保护自身免疫性糖尿病。用合成的TLR 2激动剂治疗糖尿病前期小鼠减少了T1 D，增加了CD 4 + CD 25 + TlD的数量和功能，也赋予了树突状细胞（DC）致耐受性。TLR 2连接还促进了与DC一起培养的TcR的扩增，并改善了其预防疾病的能力。淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染对T1 D的保护作用依赖于TLR 2。野生型小鼠中LCMV可显著增加CD 4 + CD 25 + TGF-beta的表达，其表达量也显著高于TLR 2缺陷型小鼠。此外，体内LCMV感染或体外LCMV感染的DC通过TLR 2使CD 4 + CD 25 + T细胞能够减少T1 D。我们确定了TLR 2促进免疫调节和控制幼稚或感染宿主自身免疫性糖尿病的新机制。这项工作应该有助于了解T1 D病因，并开发新的基于免疫的治疗干预措施。
Signaling through Toll-like receptor 2 (TLR2) promotes inflammation and modulates CD4+CD25+ regulatory T cells (Tregs). We assessed mechanistically how this molecule would alter immunoregulation in type 1 diabetes (T1D). We also asked whether TLR2 may be involved in our recent discovery that viral infection can protect from autoimmune diabetes by expanding and invigorating regulatory T cells (Tregs). Treatment of prediabetic mice with a synthetic TLR2 agonist diminished T1D and increased the number and function of CD4+CD25+ Tregs, also conferring dendritic cells (DCs) with tolerogenic properties. TLR2 ligation also promoted the expansion of Tregs upon culture with DCs and ameliorated their capacity to prevent the disease. Protection from T1D by lymphocytic choriomeningitis virus (LCMV) infection depended on TLR2. LCMV increased the frequency of CD4+CD25+ Tregs and their production of TGF-β more significantly in wild type than TLR2-deficient mice. Furthermore, LCMV infection in vivo or LCMV-infected DCs in vitro rendered, via TLR2, CD4+CD25+ Tregs capable of diminishing T1D. We identify novel mechanisms by which TLR2 promotes immunoregulation and controls autoimmune diabetes in naïve or infected hosts. This work should help understand T1D etiology and develop novel immune-based therapeutic interventions.
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DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
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影响因子：
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4.4
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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