Journal article
Tim-3 enhances Fc epsilon RI-proximal signaling to modulate mast cell activation
The Journal of experimental medicine, Vol.212(13), pp.2289-2304
12/14/2015
DOI: 10.1084/jem.20150388
PMCID: PMC4689164
PMID: 26598760
Abstract
T cell (or transmembrane) immunoglobulin and mucin domain protein 3 (Tim-3) has attracted significant attention as a novel immune checkpoint receptor (ICR) on chronically stimulated, often dysfunctional, T cells. Antibodies to Tim-3 can enhance antiviral and antitumor immune responses. Tim-3 is also constitutively expressed by mast cells, NK cells and specific subsets of macrophages and dendritic cells. There is ample evidence for a positive role for Tim-3 in these latter cell types, which is at odds with the model of Tim-3 as an inhibitory molecule on T cells. At this point, little is known about the molecular mechanisms by which Tim-3 regulates the function of T cells or other cell types. We have focused on defining the effects of Tim-3 ligation on mast cell activation, as these cells constitutively express Tim-3 and are activated through an ITAM-containing receptor for IgE (Fc epsilon RI), using signaling pathways analogous to those in T cells. Using a variety of gain-and loss-of-function approaches, we find that Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of Fc epsilon RI ligation.
Details
- Title: Subtitle
- Tim-3 enhances Fc epsilon RI-proximal signaling to modulate mast cell activation
- Creators
- Binh L. Phong - University of PittsburghLyndsay Avery - University of PittsburghTina L. Sumpter - University of PittsburghJacob V. Gorman - Roy J. and Lucille A. Carver College of MedicineSimon C. Watkins - University of PittsburghJohn D. Colgan - Roy J. and Lucille A. Carver College of MedicineLawrence P. Kane - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.212(13), pp.2289-2304
- DOI
- 10.1084/jem.20150388
- PMID
- 26598760
- PMCID
- PMC4689164
- NLM abbreviation
- J Exp Med
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Publisher
- Rockefeller Univ Press
- Number of pages
- 16
- Grant note
- K01AR067250 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) R56AI067544; P01AI073748; R01AI093737; R01AI054821; 1K01AR067250-01A1 / Public Health Service; United States Department of Health & Human Services; United States Public Health Service R01AI054821 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Language
- English
- Date published
- 12/14/2015
- Academic Unit
- Anatomy and Cell Biology; Immunology; Internal Medicine
- Record Identifier
- 9984284344202771
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