Editors' ChoiceAsthma/Atopic Disease

Antibodies Against TIM-1 for Asthma Therapy

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Science Translational Medicine  18 Aug 2010:
Vol. 2, Issue 45, pp. 45ec127
DOI: 10.1126/scitranslmed.3001566

Breathing is a daily struggle for 23 million asthma patients in America, one-third of whom are children. These numbers are increasing every day, and the disease is incurable despite enormous research efforts. One line of thought is that hygiene could be a contributing factor to asthma. The pathological shift from TH1 to TH2 immunity readily observed in atopic diseases such as atopic dermatitis and asthma results in the production of cytokines and chemokines that can effectively no longer fight infections, but rather induce chronic inflammatory responses. TIM-1, a member of the T cell Ig and mucin (TIM) domain family, is associated with relative susceptibility to the development of TH2-dominated immune responses such as in allergic asthma. Now, using humanized mouse models, Sonar et al. demonstrate that blocking TIM-1 by using specific antibodies could prevent asthmatic responses.

The authors specifically generated mouse models by injecting peripheral blood monocyte cells obtained from asthma patients into immunocompromised severe combined immunodeficient mice. These mice developed allergic disease characterized by human TH2 cytokine production, lung inflammation, and airway hyperresponsiveness (AHR). Administration of TIM-1 antibodies, which have been shown to bind to the cleft region to antagonize binding to specific ligands and cells, blunted proinflammatory cytokine production and AHR. These effects were mediated by suppression of TH2 cell proliferation and cytokine production. Thus, TIM-1 antagonists could emerge as an important therapy for asthma and other related TH2 immune-mediated disorders.

S. S. Sonar et al., Antagonism of TIM-1 blocks the development of disease in a humanized mouse model of allergic asthma. J. Clin. Invest. 120, 2767–2781 (2010). [Abstract]

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