Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin.
Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin.
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DOI：
10.2337/db10-0044
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发表时间：
2010-09
期刊：
影响因子：
7.7
通讯作者：
Schröppel B
中科院分区：
文献类型：
--
作者：
Lin M;Yin N;Murphy B;Medof ME;Segerer S;Heeger PS;Schröppel B
补体系统有助于自身免疫性损伤，但其参与促进自身免疫性糖尿病的发展是未知的。在这项研究中，我们的目标是确定补体C3在自身免疫性糖尿病中的作用。分析了野生型（WT）和C3缺陷小鼠多次低剂量链脲佐菌素治疗后糖尿病发展的易感性。进行骨髓嵌合体、luminex和定量逆转录PCR测定，以评价C3在该糖尿病模型形成中的表型和免疫学影响。与诱导的血糖水平升高相一致，我们记录了糖尿病WT小鼠胰岛内的旁路途径补体成分基因表达。当我们用C3缺陷小鼠重复实验时，我们观察到对疾病的完全抵抗力，这是通过没有组织学胰岛炎和没有T细胞对胰岛抗原的反应性来评估的。携带C3缺陷骨髓细胞的WT嵌合体的研究表明，骨髓细胞来源的C3，而不是血清C3，参与该模型中糖尿病的诱导。这些数据揭示了免疫细胞衍生的C3在小鼠多次低剂量链脲佐菌素诱导的糖尿病发病机制中的关键作用，并支持免疫细胞介导的糖尿病部分依赖补体的概念。
The complement system contributes to autoimmune injury, but its involvement in promoting the development of autoimmune diabetes is unknown. In this study, our goal was to ascertain the role of complement C3 in autoimmune diabetes. Susceptibility to diabetes development after multiple low-dose streptozotocin treatment in wild-type (WT) and C3-deficient mice was analyzed. Bone marrow chimeras, luminex, and quantitative reverse transcription PCR assays were performed to evaluate the phenotypic and immunologic impact of C3 in the development of this diabetes model. Coincident with the induced elevations in blood glucose levels, we documented alternative pathway complement component gene expression within the islets of the diabetic WT mice. When we repeated the experiments with C3-deficient mice, we observed complete resistance to disease, as assessed by the absence of histologic insulitis and the absence of T-cell reactivity to islet antigens. Studies of WT chimeras bearing C3-deficient bone marrow cells showed that bone marrow cell–derived C3, and not serum C3, is involved in the induction of diabetes in this model. The data reveal a key role for immune cell–derived C3 in the pathogenesis of murine multiple low-dose streptozotocin-induced diabetes and support the concept that immune cell mediated diabetes is in part complement-dependent.
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DOI：
10.1084/jem.20041967
发表时间：
2005-05-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Heeger PS;Lalli PN;Lin F;Valujskikh A;Liu J;Muqim N;Xu Y;Medof ME
通讯作者：
Medof ME
影响因子：
3.6
作者：
Kuhn, Kristine A.;Cozine, Cassy L.;Holers, V. Michael
通讯作者：
Holers, V. Michael
影响因子：
7.7
作者：
BROSKY, G;LOGOTHETOPOULOS, J
通讯作者：
LOGOTHETOPOULOS, J
影响因子：
4.4
作者：
Liu, Jinbo;Lin, Feng;Medof, M. Edward
通讯作者：
Medof, M. Edward
影响因子：
7.7
作者：
CHRISTIANSON, SW;SHULTZ, LD;LEITER, EH
通讯作者：
LEITER, EH