Antagonism of TIM-1 blocks the development of disease in a humanized mouse model of allergic asthma.

The Journal of Clinical Investigation
Sanchaita Sriwal SonarHarald Renz

Abstract

Studies in mice and humans have revealed that the T cell, immunoglobulin, mucin (TIM) genes are associated with several atopic diseases. TIM-1 is a type I membrane protein that is expressed on T cells upon stimulation and has been shown to modulate their activation. In addition to a recently described interaction with dendritic cells, TIM-1 has also been identified as a phosphatidylserine recognition molecule, and several protein ligands have been proposed. Our understanding of its activity is complicated by the possibility that TIM-1 possesses multiple and diverse binding partners. In order to delineate the function of TIM-1, we generated monoclonal antibodies directed to a cleft formed within the IgV domain of TIM-1. We have shown here that antibodies that bind to this defined cleft antagonize TIM-1 binding to specific ligands and cells. Notably, these antibodies exhibited therapeutic activity in a humanized SCID model of experimental asthma, ameliorating inflammation, and airway hyperresponsiveness. Further experiments demonstrated that the effects of the TIM-1-specific antibodies were mediated via suppression of Th2 cell proliferation and cytokine production. These results demonstrate that modulation of the TIM-1 pathway ca...Continue Reading

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Methods Mentioned

BETA
glycosylation
FACS
ELISA
bronchoalveolar
PCR
glyco­sylation
transfections
size exclusion chromatography
density gradient centrifugation
lavage

Software Mentioned

FloJo

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