한빛사논문
- 조회433
Youn Jung Choi1,2,7, Ji-Seung Yoo2,3,7, Kyle Jung1,2, Logan Rice1, Dokyun Kim1,2, Violetta Zlojutro4, Matthew Frimel4, Evan Madden4, Un Yung Choi1,2, Suan-Sin Foo1,2, Younho Choi1,2,5, Zhongyi Jiang1,2, Holly Johnson1, Mi-Jeong Kwak1, Seokmin Kang1, Brian Hong1, Gil Ju Seo1,2, Stephanie Kim1,2, Shin-Ae Lee1,2, Samad Amini-Bavil-Olyaee2,6, Hadi Maazi2, Omid Akbari 2, Kewal Asosingh4 & Jae U. Jung1,2,5
1Department of Cancer Biology, Infection Biology Program, and Global Center for Pathogen and Human Health Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
2Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
3School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, South Korea.
4Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
5Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA.
6Biosafety Development Group, Cellular Sciences Department, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
7These authors contributed equally: Youn Jung Choi, Ji-Seung Yoo.
Corresponding authors : Correspondence to Youn Jung Choi or Jae U. Jung.
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.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-04-14)
- 국내+국외 연구진
- 생명과학 > 면역학
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