Toll-like Receptor 2 Senses β-Cell Death and Contributes to the Initiation of Autoimmune Diabetes

Hun Sik Kim, Myoung Sook Han, Kun Wook Chung, Sunshin Kim, Eunshil Kim, Myoung Joo Kim, Eunkyeong Jang, Hyun Ah Lee, Jeehee Youn, Shizuo Akira, Myung Shik Lee

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152 Scopus citations

Abstract

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 β-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 β-cell death and its sensing via TLR2 may be an initial event for the stimulation of antigen-presenting cells and development of autoimmune diabetes.

Original languageEnglish
Pages (from-to)321-333
Number of pages13
JournalImmunity
Volume27
Issue number2
DOIs
StatePublished - 2007 Aug 24

Keywords

  • CELLIMMUNO
  • HIMDISEASE

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    Kim, H. S., Han, M. S., Chung, K. W., Kim, S., Kim, E., Kim, M. J., Jang, E., Lee, H. A., Youn, J., Akira, S., & Lee, M. S. (2007). Toll-like Receptor 2 Senses β-Cell Death and Contributes to the Initiation of Autoimmune Diabetes. Immunity, 27(2), 321-333. https://doi.org/10.1016/j.immuni.2007.06.010