CMRF35-like molecule 1 (CLM-1) regulates eosinophil homeostasis by suppressing cellular chemotaxis

Mucosal Immunol. 2014 Mar;7(2):292-303. doi: 10.1038/mi.2013.47. Epub 2013 Jul 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / immunology
  • Adipose Tissue / metabolism
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Chemokine CCL11 / pharmacology
  • Chemokine CCL24 / pharmacology
  • Chemokine CCL3 / pharmacology
  • Chemotaxis / drug effects
  • Chemotaxis / physiology*
  • Colon / immunology
  • Colon / metabolism
  • Eosinophils / drug effects
  • Eosinophils / immunology*
  • Eosinophils / metabolism*
  • Homeostasis*
  • Humans
  • Leukotriene B4 / pharmacology
  • Ligands
  • Mice
  • Mice, Knockout
  • Protein Binding
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Respiratory Hypersensitivity / immunology
  • Respiratory Hypersensitivity / metabolism


  • CLM-1 protein, mouse
  • Chemokine CCL11
  • Chemokine CCL24
  • Chemokine CCL3
  • Ligands
  • Receptors, Immunologic
  • Leukotriene B4