Linked Life Data

17277130

Source:http://linkedlifedata.com/resource/pubmed/id/17277130

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pubmed-article:17277130pubmed:abstractTextThe TAPR locus containing the TIM gene family is implicated in the development of atopic inflammation in mouse, and TIM-1 allelic variation has been associated with the incidence of atopy in human patient populations. In this study, we show that manipulation of the TIM-1 pathway influences airway inflammation and pathology. Anti-TIM-1 mAbs recognizing distinct epitopes differentially modulated OVA-induced lung inflammation in the mouse. The epitopes recognized by these Abs were mapped, revealing that mAbs to both the IgV and stalk domains of TIM-1 have therapeutic activity. Unexpectedly, mAbs recognizing unique epitopes spanning exon 4 of the mucin/stalk domains exacerbated immune responses. Using Ag recall response studies, we demonstrate that the TIM-1 pathway acts primarily by modulating the production of T(H)2 cytokines. Furthermore, ex vivo cellular experiments indicate that TIM-1 activity controls CD4(+) T cell activity. These studies validate the genetic hypothesis that the TIM-1 locus is linked to the development of atopic disease and suggest novel therapeutic strategies for targeting asthma and other atopic disorders.lld:pubmed
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pubmed-article:17277130pubmed:articleTitleEpitope-dependent effect of anti-murine TIM-1 monoclonal antibodies on T cell activity and lung immune responses.lld:pubmed
pubmed-article:17277130pubmed:affiliationBiogen Idec Incorporated, Cambridge, MA 02142, USA.lld:pubmed
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