Lung-specific MCEMP1 functions as an adaptor for KIT to promote SCF-mediated mast cell proliferation

Nat Commun. 2023 Apr 11;14(1):2045. doi: 10.1038/s41467-023-37873-3.

Abstract

Lung mast cells are important in host defense, and excessive proliferation or activation of these cells can cause chronic inflammatory disorders like asthma. Two parallel pathways induced by KIT-stem cell factor (SCF) and FcεRI-immunoglobulin E interactions are critical for the proliferation and activation of mast cells, respectively. Here, we report that mast cell-expressed membrane protein1 (MCEMP1), a lung-specific surface protein, functions as an adaptor for KIT, which promotes SCF-mediated mast cell proliferation. MCEMP1 elicits intracellular signaling through its cytoplasmic immunoreceptor tyrosine-based activation motif and forms a complex with KIT to enhance its autophosphorylation and activation. Consequently, MCEMP1 deficiency impairs SCF-induced peritoneal mast cell proliferation in vitro and lung mast cell expansion in vivo. Mcemp1-deficient mice exhibit reduced airway inflammation and lung impairment in chronic asthma mouse models. This study shows lung-specific MCEMP1 as an adaptor for KIT to facilitate SCF-mediated mast cell proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma*
  • Cell Proliferation
  • Lung / metabolism
  • Mice
  • Proto-Oncogene Proteins c-kit / metabolism
  • Stem Cell Factor* / metabolism

Substances

  • Proto-Oncogene Proteins c-kit
  • Stem Cell Factor
  • Mcemp1 protein, mouse