Anti-T-cell Ig and mucin domain-containing protein 1 antibody decreases TH2 airway inflammation in a mouse model of asthma

Jeffrey A. Encinas, Edith M. Janssen, David B. Weiner, Sandra A. Calarota, Daisy Nieto, Thomas Moll, Dennis J. Carlo, Ronald B. Moss

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The T-cell Ig and mucin domain-containing (TIM) gene locus has been linked to differences in TH2 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 TH2 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 TH2 cytokines IL-10 and IL-13 by cells from the draining lymph nodes. The TH1 cytokine IFN-γ 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.

Original languageEnglish
Pages (from-to)1343-1349
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume116
Issue number6
DOIs
Publication statusPublished - Dec 2005

Keywords

  • Asthma
  • Cytokines
  • T-cell Ig and mucin domain-containing protein
  • T2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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