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Am. J. Respir. Crit. Care Med., Published Online: February 02, 2018 | https://doi.org/10.1164/rccm.201703-0532OC
Activated Leukocyte Cell Adhesion Molecule Stimulates the T Cell Response in Allergic Asthma
Mi Na Kim1, Jung Yeon Hong1, Doo Hee Shim2, In Suk Sol1, Yun Seon Kim1, Ji Hyun Lee3, Kyung Won Kim1, Jae Myun Lee2, Myung Hyun Sohn1*
1Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
1Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
2Department of Microbiology and Immunology, Yonsei University College of Medicine,Seoul, Republic of Korea.
3Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul, Korea.
*Author for correspondence : Myung Hyun Sohn, MD, PhD
*Author for correspondence : Myung Hyun Sohn, MD, PhD
Department of Pediatrics, Yonsei University College of Medicine 134 Sinchon-Dong, Seoul 120-752, Korea
Abstract
Rationale: 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: This study 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 co-cultures with dendritic cells (DCs). Bone marrow-derived (BM)DCs from WT and ALCAM-/- mice were cultured and adoptively transferred to OT-II mice either for OVA sensitization or challenge. An anti-ALCAM antibody was administered to assess its therapeutic potential. ALCAM levels in the sputum and serum of children with asthma were quantified by enzyme-linked immunosorbent assay.
Measurements and Main Results: Inflammatory responses were lower in ALCAM-/- mice as compared with WT mice, and T cells co-cultured with DCs from ALCAM-/- mice showed reduced proliferation relative to those co-cultured with DCs from WT mice. A decreased inflammatory response was observed upon adoptive transfer of BMDCs from ALCAM-/- mice as compared with that observed following transfer of BMDCs from WT mice. Additionally, anti-ALCAM antibody-treated mice showed a reduced inflammatory response, and sputum and serum ALCAM levels were higher in children with asthma than in control subjects.
Conclusion: ALCAM contributes to OVA-induced allergic asthma by stimulating T cell activation and proliferation, suggesting it as a potential therapeutic target for allergic asthma.
Keywords: ALCAM, Asthma, Immune synapse, Dendritic cell, T cell proliferation
Objectives: This study 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 co-cultures with dendritic cells (DCs). Bone marrow-derived (BM)DCs from WT and ALCAM-/- mice were cultured and adoptively transferred to OT-II mice either for OVA sensitization or challenge. An anti-ALCAM antibody was administered to assess its therapeutic potential. ALCAM levels in the sputum and serum of children with asthma were quantified by enzyme-linked immunosorbent assay.
Measurements and Main Results: Inflammatory responses were lower in ALCAM-/- mice as compared with WT mice, and T cells co-cultured with DCs from ALCAM-/- mice showed reduced proliferation relative to those co-cultured with DCs from WT mice. A decreased inflammatory response was observed upon adoptive transfer of BMDCs from ALCAM-/- mice as compared with that observed following transfer of BMDCs from WT mice. Additionally, anti-ALCAM antibody-treated mice showed a reduced inflammatory response, and sputum and serum ALCAM levels were higher in children with asthma than in control subjects.
Conclusion: ALCAM contributes to OVA-induced allergic asthma by stimulating T cell activation and proliferation, suggesting it as a potential therapeutic target for allergic asthma.
Keywords: ALCAM, Asthma, Immune synapse, Dendritic cell, T cell proliferation
논문정보
- Research article
- 2018년 02월 (BRIC 등록일 2018-02-22)
- 국내 연구진
- 의약학 > 면역의학
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