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Anti-T-cell Ig and mucin domain-containing protein 1 antibody decreases TH2 airway inflammation in a mouse model of asthma. | LitMetric
Background : The T-cell Ig and mucin domain-containing (TIM) gene locus has been linked to differences in T(H)2 responsiveness and asthma susceptibility in mice. The homologous locus in human subjects harbors the gene for TIM-1, which encodes a receptor for hepatitis A virus and has been linked with decreased susceptibility to atopic disease in hepatitis A virus-seropositive individuals.Objective : We investigated the effects of administering antibodies against TIM-1 in a mouse model of allergic asthma to determine whether the treatment could downregulate T(H)2 cytokines and reduce pulmonary inflammation.Methods : BALB/c mice were sensitized and challenged with ovalbumin to induce airway inflammation. Before the ovalbumin challenge, mice were treated with anti-TIM-1 mAb or a control antibody.Results : Administration of anti-TIM-1 antibody to mice after ovalbumin sensitization and before ovalbumin challenge results in a significant decrease in inflammatory cells in bronchoalveolar lavage fluid compared with administration of a control antibody. The decrease is accompanied by significantly lower antigen-specific production of the T(H)2 cytokines IL-10 and IL-13 by cells from the draining lymph nodes. The T(H)1 cytokine IFN-gamma appears to be unaffected. Analysis of the lungs shows that goblet cell hyperplasia and mucus production and the expression of IL-10 are markedly decreased in anti-TIM-1-treated mice.Conclusion : The results indicate that anti-TIM-1 might offer a novel approach to treating asthma.
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