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

Youn Jung Choi (), Ji-Seung Yoo, Kyle Jung, Logan Rice, Dokyun Kim, Violetta Zlojutro, Matthew Frimel, Evan Madden, Un Yung Choi, Suan-Sin Foo, Younho Choi, Zhongyi Jiang, Holly Johnson, Mi-Jeong Kwak, Seokmin Kang, Brian Hong, Gil Ju Seo, Stephanie Kim, Shin-Ae Lee, Samad Amini-Bavil-Olyaee, Hadi Maazi, Omid Akbari, Kewal Asosingh and Jae U. Jung ()
Additional contact information
Youn Jung Choi: Lerner Research Institute, Cleveland Clinic
Ji-Seung Yoo: University of Southern California
Kyle Jung: Lerner Research Institute, Cleveland Clinic
Logan Rice: Lerner Research Institute, Cleveland Clinic
Dokyun Kim: Lerner Research Institute, Cleveland Clinic
Violetta Zlojutro: Lerner Research Institute, Cleveland Clinic
Matthew Frimel: Lerner Research Institute, Cleveland Clinic
Evan Madden: Lerner Research Institute, Cleveland Clinic
Un Yung Choi: Lerner Research Institute, Cleveland Clinic
Suan-Sin Foo: Lerner Research Institute, Cleveland Clinic
Younho Choi: Lerner Research Institute, Cleveland Clinic
Zhongyi Jiang: Lerner Research Institute, Cleveland Clinic
Holly Johnson: Lerner Research Institute, Cleveland Clinic
Mi-Jeong Kwak: Lerner Research Institute, Cleveland Clinic
Seokmin Kang: Lerner Research Institute, Cleveland Clinic
Brian Hong: Lerner Research Institute, Cleveland Clinic
Gil Ju Seo: Lerner Research Institute, Cleveland Clinic
Stephanie Kim: Lerner Research Institute, Cleveland Clinic
Shin-Ae Lee: Lerner Research Institute, Cleveland Clinic
Samad Amini-Bavil-Olyaee: University of Southern California
Hadi Maazi: University of Southern California
Omid Akbari: University of Southern California
Kewal Asosingh: Lerner Research Institute, Cleveland Clinic
Jae U. Jung: Lerner Research Institute, Cleveland Clinic

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37873-3

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