Mi Na Kim1,2,3,4, Jung Yeon Hong1,2,3,4, Doo Hee Shim5, In Suk Sol1,2,3,4, Yun Seon Kim1,2,3,4, Ji Hyun Lee6, Kyung Won Kim1,2,3,4, Jae Myun Lee4,5, Myung Hyun Sohn1,2,3,4. 1. 1 Department of Pediatrics. 2. 2 Institute of Allergy. 3. 3 Severance Hospital. 4. 4 Brain Korea 21 PLUS Project for Medical Science, and. 5. 5 Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Republic of Korea; and. 6. 6 Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Abstract
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.
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.
Authors: Eun Gyul Kim; Ji Su Leem; Seung Min Baek; Hye Rin Kim; Kyung Won Kim; Mi Na Kim; Myung Hyun Sohn Journal: Allergy Asthma Immunol Res Date: 2022-07 Impact factor: 5.096
Authors: Wei Wang; Jonathan A Cohen; Antonia Wallrapp; Kenneth G Trieu; Juliana Barrios; Fengzhi Shao; Nandini Krishnamoorthy; Vijay K Kuchroo; Matthew R Jones; Alan Fine; Yan Bai; Xingbin Ai Journal: Immunity Date: 2019-11-19 Impact factor: 31.745
Authors: James R Byrnes; Amy M Weeks; Eric Shifrut; Julia Carnevale; Lisa Kirkemo; Alan Ashworth; Alexander Marson; James A Wells Journal: Mol Cell Proteomics Date: 2022-02-23 Impact factor: 5.911