Apoptotic Cells Activate NKT Cells through T Cell Ig-Like Mucin-Like-1 Resulting in Airway Hyperreactivity

作者：Lee Hyun Hee; Meyer Everett H; Goya Sho; Pichavant Muriel; Kim Hye Young; Bu Xia; Umetsu Sarah E; Jones Jennifer C; Savage Paul B; Iwakura Yoichiro; Casasnovas Jose M; Kaplan Gerardo; Freeman Gordon J; DeKruyff Rosemarie H; Umetsu Dale T^*

来源：The Journal of Immunology, 2010, 185(9): 5225-5235.

DOI：10.4049/jimmunol.1001116

T cell Ig-like mucin-like-1 (TIM-1) is an important asthma susceptibility gene, but the immunological mechanisms by which TIM-1 functions remain uncertain. TIM-1 is also a receptor for phosphatidylserine (PtdSer), an important marker of cells undergoing programmed cell death, or apoptosis. We now demonstrate that NKT cells constitutively express TIM-1 and become activated by apoptotic cells expressing PtdSer. TIM-1 recognition of PtdSer induced NKT cell activation, proliferation, and cytokine production. Moreover, the induction of apoptosis in airway epithelial cells activated pulmonary NKT cells and unexpectedly resulted in airway hyperreactivity, a cardinal feature of asthma, in an NKT cell-dependent and TIM-1-dependent fashion. These results suggest that TIM-1 serves as a pattern recognition receptor on NKT cells that senses PtdSer on apoptotic cells as a damage-associated molecular pattern. Furthermore, these results provide evidence for a novel innate pathway that results in airway hyperreactivity and may help to explain how TIM-1 and NKT cells regulate asthma. The Journal of Immunology, 2010, 185: 5225-5235.

• 出版日期2010-11-1
• 单位河北医科大学