Details

Autor(en) / Beteiligte

• Kim, Hye Young, PhD
• Chang, Ya-Jen, PhD
• Chuang, Ya-Ting, PhD
• Lee, Hyun-Hee, PhD
• Kasahara, David I., PhD
• Martin, Thomas, MD, PhD
• Hsu, Joyce T., MD
• Savage, Paul B., PhD
• Shore, Stephanie A., PhD
• Freeman, Gordon J., PhD
• DeKruyff, Rosemarie H., PhD
• Umetsu, Dale T., MD, PhD

Titel

T-cell immunoglobulin and mucin domain 1 deficiency eliminates airway hyperreactivity triggered by the recognition of airway cell death

Ist Teil von

• Journal of allergy and clinical immunology, 2013-08, Vol.132 (2), p.414-425.e6

Ort / Verlag

New York, NY: Mosby, Inc

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.