Toll-like receptor 2 senses β-cell death and contributes to the initiation of autoimmune diabetes

被引:181
作者
Kim, Hun Sik
Han, Myoung Sook
Chung, Kun Wook
Kim, Sunshin
Kim, Eunshil
Kim, Myoung Joo
Jang, Eunkyeong
Lee, Hyun Ah
Youn, Jeehee
Akira, Shizuo
Lee, Myung-Shik [1 ]
机构
[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med, Seoul 135710, South Korea
[2] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Canc Res Ctr, Seoul 135710, South Korea
[3] Hanyang Univ, Coll Med, Dept Anat & Cell Biol, Seoul 133791, South Korea
[4] Osaka Univ, Res Inst Microbial Dis, Dept Host Def, Suita, Osaka 5650871, Japan
关键词
D O I
10.1016/j.immuni.2007.06.010
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Although it is established that defective clearance and, hence, increased accumulation of apoptotic cells can lead to autoimmunity, the mechanism by which this occurs remains elusive. Here, we observed that apoptotic cells undergoing secondary necrosis but not intact apoptotic cells provoked substantial immune responses, which were mediated through the toll-like receptor 2 (TLR2) pathway. The development of autoimmune diabetes was markedly inhibited in Tlr2(-/-) mice but not in Tlr4(-/-) mice, showing that TLR2 plays an important role in the initiation of the disease. Apoptotic P-cell injury could stimulate the priming of diabetogenic T cells through a TLR2-dependent, but TLR4-independent, activation of antigen-presenting cells. These findings suggest that beta-cell death and its sensing via TLR2 may be an initial event for the stimulation of antigen-presenting cells and development of autoimmune diabetes.
引用
收藏
页码:321 / 333
页数:13
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