活化白细胞粘附分子刺激过敏性哮喘的T细胞应答
2018/10/31
摘要
背景: 活化白细胞粘附分子（Activated leukocyte cell-adhesion molecule, ALCAM）是抗原分化簇6（cluster of differentiation 6，CD6）的配体，其对于稳定免疫突触和诱导T细胞活化与增殖至关重要。
目的: 本研究探索了ALCAM在过敏性哮喘炎症发展中的作用。
方法: 在野生型（WT）和ALCAM缺陷型（ALCAM -/- ）小鼠中，建立卵蛋白（OVA）诱导的过敏性哮喘模型。与树突状细胞（DC）共培养，以评估T细胞增殖。WT和ALCAM -/- 小鼠，用骨髓来源的（BM）DC进行培养，并过继转移给OT-II小鼠，用于OVA致敏或激发。使用抗ALCAM抗体以评估其治疗潜力。通过酶联免疫吸附测定法（ELISA），检测哮喘儿童痰液与血清中ALCAM水平。
结果: 与WT小鼠相比，ALCAM -/- 小鼠的炎性应答较低；与来自WT小鼠DC共培养比较，来自ALCAM -/- 小鼠DC共培养的T细胞，其增殖活性降低。与从WT小鼠过继转移BMDC后比较，从ALCAM -/- 小鼠过继转移BMDC后，观察到其炎症反应降低。此外，使用抗ALCAM抗体治疗的小鼠显示出炎症反应减轻。哮喘患儿的痰液与血清中ALCAM水平高于对照组。
结论: ALCAM通过刺激T细胞活化与增殖，促进OVA诱导的过敏性哮喘，表明它可能成为过敏性哮喘的潜在治疗靶标。
Activated leukocyte cell adhesion molecule stimulates the T cell response in allergic asthma
Kim MN, Hong JY, Shim DH, Sol IS, Kim YS, Lee JH, Kim KW, Lee JM, Sohn MH.
Am J Respir Crit Care Med. 2018;197(8):994-1008.
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 cocultures 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.
背景: 活化白细胞粘附分子（Activated leukocyte cell-adhesion molecule, ALCAM）是抗原分化簇6（cluster of differentiation 6，CD6）的配体，其对于稳定免疫突触和诱导T细胞活化与增殖至关重要。
目的: 本研究探索了ALCAM在过敏性哮喘炎症发展中的作用。
方法: 在野生型（WT）和ALCAM缺陷型（ALCAM -/- ）小鼠中，建立卵蛋白（OVA）诱导的过敏性哮喘模型。与树突状细胞（DC）共培养，以评估T细胞增殖。WT和ALCAM -/- 小鼠，用骨髓来源的（BM）DC进行培养，并过继转移给OT-II小鼠，用于OVA致敏或激发。使用抗ALCAM抗体以评估其治疗潜力。通过酶联免疫吸附测定法（ELISA），检测哮喘儿童痰液与血清中ALCAM水平。
结果: 与WT小鼠相比，ALCAM -/- 小鼠的炎性应答较低；与来自WT小鼠DC共培养比较，来自ALCAM -/- 小鼠DC共培养的T细胞，其增殖活性降低。与从WT小鼠过继转移BMDC后比较，从ALCAM -/- 小鼠过继转移BMDC后，观察到其炎症反应降低。此外，使用抗ALCAM抗体治疗的小鼠显示出炎症反应减轻。哮喘患儿的痰液与血清中ALCAM水平高于对照组。
结论: ALCAM通过刺激T细胞活化与增殖，促进OVA诱导的过敏性哮喘，表明它可能成为过敏性哮喘的潜在治疗靶标。
(张红萍 王刚 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Am J Respir Crit Care Med.2018;197(8):994-1008.）
（Am J Respir Crit Care Med.2018;197(8):994-1008.）
Activated leukocyte cell adhesion molecule stimulates the T cell response in allergic asthma
Kim MN, Hong JY, Shim DH, Sol IS, Kim YS, Lee JH, Kim KW, Lee JM, Sohn MH.
Am J Respir Crit Care Med. 2018;197(8):994-1008.
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 cocultures 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.
