CMRF35-like molecule 1 (CLM-1) regulates eosinophil homeostasis by suppressing cellular chemotaxis
| Autor: | M. van Lookeren Campagne, Danielle Karo-Atar, Alon Y. Hershko, Dana Shik, Itay Moshkovits, B Bernshtein, Ariel Munitz, Michal Itan |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Chemokine CCL11
Eotaxin Colon Immunology Eosinophil homeostasis Apoptosis Ligands Leukotriene B4 Mice 03 medical and health sciences 0302 clinical medicine Eosinophil migration Respiratory Hypersensitivity medicine Animals Homeostasis Humans Immunology and Allergy Eosinophilia Receptors Immunologic Chemokine CCL3 030304 developmental biology Mice Knockout 0303 health sciences Eosinophil cationic protein biology Chemotaxis Chemokine CCL24 respiratory system Eosinophil 3. Good health Eosinophils medicine.anatomical_structure Adipose Tissue Major basic protein biology.protein Eosinophil chemotaxis medicine.symptom Protein Binding 030215 immunology |
| Zdroj: | Mucosal Immunology. 7:292-303 |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/mi.2013.47 |
| Popis: | 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 B₄ (LTB₄)- and macrophage inflammatory protein-1α (MIP-1α)-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. |
| Databáze: | OpenAIRE |
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