| First Author | Kim HY | Year | 2013 |
| Journal | J Allergy Clin Immunol | Volume | 132 |
| Issue | 2 | Pages | 414-25.e6 |
| PubMed ID | 23672783 | Mgi Jnum | J:315278 |
| Mgi Id | MGI:6829983 | Doi | 10.1016/j.jaci.2013.03.025 |
| Citation | Kim HY, et al. (2013) T-cell immunoglobulin and mucin domain 1 deficiency eliminates airway hyperreactivity triggered by the recognition of airway cell death. J Allergy Clin Immunol 132(2):414-25.e6 |
| abstractText | BACKGROUND: Studies of asthma have been limited by a poor understanding of how nonallergic environmental exposures, such as air pollution and infection, are translated in the lung into inflammation and wheezing. OBJECTIVE: Our goal was to understand the mechanism of nonallergic asthma that leads to airway hyperreactivity (AHR), a cardinal feature of asthma independent of adaptive immunity. METHOD: We examined mouse models of experimental asthma in which AHR was induced by respiratory syncytial virus infection or ozone exposure using mice deficient in T-cell immunoglobulin and mucin domain 1 (TIM1/HAVCR1), an important asthma susceptibility gene. RESULTS: TIM1(-/-) mice did not have airways disease when infected with RSV or when repeatedly exposed to ozone, a major component of air pollution. On the other hand, the TIM1(-/-) mice had allergen-induced experimental asthma, as previously shown. The RSV- and ozone-induced pathways were blocked by treatment with caspase inhibitors, indicating an absolute requirement for programmed cell death and apoptosis. TIM-1-expressing, but not TIM-1-deficient, natural killer T cells responded to apoptotic airway epithelial cells by secreting cytokines, which mediated the development of AHR. CONCLUSION: We defined a novel pathway in which TIM-1, a receptor for phosphatidylserine expressed by apoptotic cells, drives the development of asthma by sensing and responding to injured and apoptotic airway epithelial cells. |
