• Hyun-Hee Lee, Everett H Meyer, Sho Goya, Muriel Pichavant, Hye Young Kim, Xia Bu, Sarah E Umetsu, Jennifer C Jones, Paul B Savage, Yoichiro Iwakura, Jose M Casasnovas, Gerardo Kaplan, Gordon J Freeman, Rosemarie H DeKruyff, and Dale T Umetsu.
• Division of Immunology and Allergy, Department of Pediatrics, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
• J. Immunol. 2010 Nov 1; 185 (9): 5225-35.

AbstractT 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.

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