期刊
MUCOSAL IMMUNOLOGY
卷 7, 期 2, 页码 292-303出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2013.47
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资金
- Israel Science Foundation [1084/10, 955/11]
- Joan and Jaime Constantiner Institute for Molecular Genetics
- FP7 Marie-Curie Reintegration grant [256311]
- US-Israel Binational Science Foundation [2009222, 2011244]
- Israel Cancer Research Foundation Research Career Development Award
- Dream Ideas Djerassi-Elias Institute of Oncology Research Fund
- Tel-Aviv University
Eosinophil accumulation in health and disease is a hallmark characteristic of mucosal immunity and type 2 helper T cell (Th2) inflammation. Eotaxin-induced CCR3 (chemokine (C-C motif) receptor 3) signaling has a critical role in eosinophil chemotactic responses. Nevertheless, the expressions of immunoreceptor tyrosine-based inhibitory motif-bearing receptors such as CMRF35-like molecule-1 (CLM-1) and their ability to govern eosinophil migration are largely unknown. We now report that CLM-1 (but not CLM-8) is highly and distinctly expressed by colonic and adipose tissue eosinophils. Furthermore, Clm1(-/-) mice display elevated baseline tissue eosinophilia. CLM-1 negatively regulated eotaxin-induced eosinophil responses including eosinophil chemotaxis, actin polymerization, calcium influx, and extracellular signal-regulated kinase (ERK)-1/2, but not p38 phosphorylation. Addition of CLM-1 ligand (e. g., phosphatidylserine) rendered wild-type eosinophils hypochemotactic in vitro and blockade of CLM-1/ligand interactions rendered wild-type eosinophils hyperchemotactic in vitro and in vivo in a model of allergic airway disease. Interestingly, suppression of cellular recruitment via CLM-1 was specific to eosinophils and eotaxin, as leukotriene B-4 (LTB4)- and macrophage inflammatory protein-1 alpha (MIP-1 alpha)-induced eosinophil and neutrophil migration were not negatively regulated by CLM-1. Finally, peripheral blood eosinophils obtained from allergic rhinitis patients displayed elevated CLM-1/CD300f levels. These data highlight CLM-1 as a novel regulator of eosinophil homeostasis and demonstrate that eosinophil accumulation is constantly governed by CLM-1, which negatively regulates eotaxin-induced eosinophil responses.
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