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Mast cell activation is enhanced by Tim1: Tim4 interaction but not by Tim-1 antibodies [version 2; referees: 2 approved]

Phong, B and Kane, LP (2016) Mast cell activation is enhanced by Tim1: Tim4 interaction but not by Tim-1 antibodies [version 2; referees: 2 approved]. F1000Research, 5. ISSN 2046-1402

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Abstract

© 2016 Phong B and Kane LP. Polymorphisms in the T cell (or transmembrane) immunoglobulin and mucin domain 1 (TIM-1) gene, particularly in the mucin domain, have been associated with atopy and allergic diseases in mice and human. Genetic- and antibody-mediated studies revealed that Tim-1 functions as a positive regulator of Th2 responses, while certain antibodies to Tim-1 can exacerbate or reduce allergic lung inflammation. Tim-1 can also positively regulate the function of B cells, NKT cells, dendritic cells and mast cells. However, the precise molecular mechanisms by which Tim-1 modulates immune cell function are currently unknown. In this study, we have focused on defining Tim-1-mediated signaling pathways that enhance mast cell activation through the high affinity IgE receptor (FceRI). Using a Tim-1 mouse model lacking the mucin domain (Tim-1 Dmucin;), we show for the first time that the polymorphic Tim-1 mucin region is dispensable for normal mast cell activation. We further show that Tim-4 cross-linking of Tim-1 enhances select signaling pathways downstream of FceRI in mast cells, including mTOR-dependent signaling, leading to increased cytokine production but without affecting degranulation.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Phong, Bblp37@pitt.eduBLP37
Kane, LPlkane@pitt.eduLKANE
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
ReviewerAugust, AveryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
ReviewerWilson, Bridget SUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 January 2016
Date Type: Publication
Journal or Publication Title: F1000Research
Volume: 5
DOI or Unique Handle: 10.12688/f1000research.8132.2
Schools and Programs: School of Medicine > Immunology
Refereed: Yes
ISSN: 2046-1402
Date Deposited: 09 Aug 2016 20:00
Last Modified: 02 Feb 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/29115

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