The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.
The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.
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A 类清道夫受体在自身免疫 NOD 小鼠糖尿病发展中的双重作用。
DOI：
10.1371/journal.pone.0109531
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yokono K
中科院分区：
文献类型：
--
作者：
Shimizu M;Yasuda H;Hara K;Takahashi K;Nagata M;Yokono K
人1型糖尿病是一种自身免疫性疾病，其由T细胞对胰腺β细胞的自身反应性破坏引起。抗原呈递细胞包括树突细胞和巨噬细胞是激活和抑制抗原特异性T细胞所必需的。已经表明树突状细胞通过清道夫受体A类（SR-A）从活细胞摄取抗原可能是重要的。然而，SR-A在自身免疫性疾病中的作用尚不清楚。在这项研究中，与NOD小鼠相比，SR-A−/−非肥胖糖尿病（NOD）小鼠表现出显著的胰岛炎减轻，胰岛素自身抗体水平降低，糖尿病发展受到抑制。我们还发现，与接受低剂量poly（I ∶ C）治疗的疾病抵抗NOD小鼠相比，接受低剂量poly（I ∶ C）治疗的SR-A−/− NOD小鼠的糖尿病进展显著加快。此外，与未治疗的SR-A −/− NOD小鼠相比，注射高剂量poly（I∶C）模拟急性RNA病毒感染显著加速了年轻SR-A −/− NOD小鼠的糖尿病发展。与未处理的SR-A −/− NOD小鼠相比，用poly（I∶C）处理的SR-A −/− NOD小鼠中的致病细胞（包括CD 4 + CD 25+活化的T细胞）增加更多。这些结果表明，即使在对糖尿病有抵抗力的受试者中，病毒感染也可能加速糖尿病的发展。总之，我们的研究表明，SR-A−/− NOD小鼠的糖尿病进展受到抑制，并且即使在SR-A−/− NOD小鼠中，poly（I∶C）治疗也可以在年轻小鼠中诱导糖尿病发展的加速。这些结果表明，抗原呈递细胞如树突状细胞上的SR-A可能在稳态下起不利作用，而在轻度感染中起保护作用。我们的研究结果表明，SR-A可能是改善1型糖尿病治疗策略的重要靶点。
Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic β cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A) may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A−/− nonobese diabetic (NOD) mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A−/− NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I∶C)) was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I∶C). In addition, injection of high-dose poly(I∶C) to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A−/− NOD mice compared with untreated SR-A−/− NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A−/− NOD mice treated with poly(I∶C) than in untreated SR-A−/− NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A−/− NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I∶C) treatment even in SR-A−/− NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.
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影响因子：
6.7
作者：
Dansako H;Yamane D;Welsch C;McGivern DR;Hu F;Kato N;Lemon SM
通讯作者：
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影响因子：
6.7
作者：
DeWitte-Orr SJ;Collins SE;Bauer CM;Bowdish DM;Mossman KL
通讯作者：
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DOI：
10.4049/jimmunol.1201680
发表时间：
2013-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Haasken S;Auger JL;Taylor JJ;Hobday PM;Goudy BD;Titcombe PJ;Mueller DL;Binstadt BA
通讯作者：
Binstadt BA
影响因子：
7.7
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影响因子：
4.8
作者：
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通讯作者：
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