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Activated Leukocyte Cell Adhesion Molecule Stimulates the T-Cell Response in Allergic Asthma

 Mi Na Kim  ;  Jung Yeon Hong  ;  Doo Hee Shim  ;  In Suk Sol  ;  Yun Seon Kim  ;  Ji Hyun Lee  ;  Kyung Won Kim  ;  Jae Myun Lee  ;  Myung Hyun Sohn 
 American Journal of Respiratory and Critical Care Medicine, Vol.197(8) : 994-1008, 2018 
Journal Title
 American Journal of Respiratory and Critical Care Medicine 
Issue Date
T-cell proliferation ; activated leukocyte cell adhesion molecule ; asthma ; dendritic cell ; immune synapse
RATIONALE: The activated leukocyte cell adhesion molecule (ALCAM) is a cluster of differentiation 6 ligand that is important for stabilizing the immunological synapse and inducing T-cell activation and proliferation. OBJECTIVES: In this study, we investigated the role of ALCAM in the development of inflammation in allergic asthma. METHODS: An ovalbumin (OVA)-induced allergic asthma model was established in wild-type (WT) and ALCAM-deficient (ALCAM(-/-)) mice. T-cell proliferation was evaluated in cocultures with dendritic cells (DCs). Bone marrow-derived dendritic cells (BMDCs) from WT and ALCAM(-/-) mice were cultured and adoptively transferred to OT-II mice for either OVA sensitization or challenge. An anti-ALCAM antibody was administered to assess its therapeutic potential. ALCAM concentrations in the sputum and serum of children with asthma were quantified by ELISA. MEASUREMENTS AND MAIN RESULTS: Inflammatory responses were lower in ALCAM(-/-) mice than in WT mice, and T cells cocultured with DCs from ALCAM(-/-) mice showed reduced proliferation relative to those cocultured with DCs from WT mice. A decreased inflammatory response was observed upon adoptive transfer of BMDCs from ALCAM(-/-) mice as compared with that observed after transfer of BMDCs from WT mice. In addition, anti-ALCAM antibody-treated mice showed a reduced inflammatory response, and sputum and serum ALCAM concentrations were higher in children with asthma than in control subjects. CONCLUSIONS: ALCAM contributes to OVA-induced allergic asthma by stimulating T-cell activation and proliferation, suggesting it as a potential therapeutic target for allergic asthma.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
김경원(Kim, Kyung Won) ORCID logo https://orcid.org/0000-0003-4529-6135
김미나(Kim, Mina) ORCID logo https://orcid.org/0000-0002-1675-0688
설인숙(Sol, In Suk) ORCID logo https://orcid.org/0000-0003-2470-9682
손명현(Sohn, Myung Hyun) ORCID logo https://orcid.org/0000-0002-2478-487X
심두희(Shim, Doo Hee) ORCID logo https://orcid.org/0000-0002-6696-7199
이재면(Lee, Jae Myun) ORCID logo https://orcid.org/0000-0002-5273-3113
홍정연(Hong, Jung Yeon) ORCID logo https://orcid.org/0000-0003-0406-9956
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