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Apoptotic Cells Activate NKT Cells through T Cell Ig-Like Mucin-Like-1 Resulting in Airway Hyperreactivity JOURNAL OF IMMUNOLOGY Lee, H., Meyer, E. H., Goya, S., Pichavant, M., Kim, H. Y., Bu, X., Umetsu, S. E., Jones, J. C., Savage, P. B., Iwakura, Y., Casasnovas, J. M., Kaplan, G., Freeman, G. J., DeKruyff, R. H., Umetsu, D. T. 2010; 185 (9): 5225-5235

Abstract

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.

View details for DOI 10.4049/jimmunol.1001116

View details for Web of Science ID 000283248700036

View details for PubMedID 20889552

View details for PubMedCentralID PMC3114419