Mast cell activation is enhanced by Tim 1 : Tim 4 interaction but not by Tim - 1 antibodies

Abstract

Polymorphisms in the T cell (or transmembrane) immunoglobulin and mucin ( ) gene, particularly in the mucin domain, have been associated domain 1 TIM-1 with atopy and allergic diseases in mice and human. Geneticand 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 ), 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. Lawrence P. Kane ( ) Corresponding author: lkane@pitt.edu Phong B and Kane LP. How to cite this article: Mast cell activation is enhanced by Tim1:Tim4 interaction but not by Tim-1 antibodies 2016, :251 (doi: ) [version 2; referees: 2 approved] F1000Research 5 10.12688/f1000research.8132.2 © 2016 Phong B and Kane LP. This is an open access article distributed under the terms of the , Copyright: Creative Commons Attribution Licence which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the (CC0 1.0 Public domain dedication). Creative Commons Zero "No rights reserved" data waiver This work was supported by PHS grant R56AI067544 to LPK. Grant information: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: No competing interests were disclosed. 01 Mar 2016, :251 (doi: ) First published: 5 10.12688/f1000research.8132.1 1,2

Cite this paper

@inproceedings{Wilson2016MastCA, title={Mast cell activation is enhanced by Tim 1 : Tim 4 interaction but not by Tim - 1 antibodies}, author={Bridget S. Wilson and Lawrence P Kane}, year={2016} }