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活化白细胞细胞黏附分子(ALCAM/CD166)在食物过敏的小鼠模型中调节 T 细胞反应。

Activated leucocyte cell adhesion molecule (ALCAM/CD166) regulates T cell responses in a murine model of food allergy.

机构信息

Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.

出版信息

Clin Exp Immunol. 2018 May;192(2):151-164. doi: 10.1111/cei.13104. Epub 2018 Feb 20.

Abstract

Food allergy is a major public health problem. Studies have shown that long-term interactions between activated leucocyte cell adhesion molecule (ALCAM/CD166) on the surface of antigen-presenting cells, and CD6, a co-stimulatory molecule, influence immune responses. However, there are currently no studies on the functions of ALCAM in food allergy. Therefore, we aimed to identify the functions of ALCAM in ovalbumin (OVA)-induced food allergy using ALCAM-deficient mice. Wild-type (WT) and ALCAM-deficient (ALCAM ) mice were sensitized intraperitoneally and with orally fed OVA. The mice were killed, and parameters related to food allergy and T helper type 2 (Th2) immune responses were analysed. ALCAM serum levels increased and mRNA expression decreased in OVA-challenged WT mice. Serum immunoglobulin (Ig)E levels, Th2 cytokine mRNA and histological injuries were higher in OVA-challenged WT mice than in control mice, and these were attenuated in ALCAM mice. T cell proliferation of total cells, CD3 CD4 T cells and activated T cells in immune tissues were diminished in OVA-challenged ALCAM mice. Proliferation of co-cultured T cells and dendritic cells (DCs) was decreased by the anti-CD6 antibody. In addition, WT mice sensitized by adoptive transfer of OVA-pulsed ALCAM BM-derived DCs showed reduced immune responses. Lastly, serum ALCAM levels were higher in children with food allergy than in control subjects. In this study, serum levels of ALCAM were elevated in food allergy-induced WT mice and children with food allergy. Moreover, immune responses and T cell activation were attenuated in OVA-challenged ALCAM mice. These results indicate that ALCAM regulates food allergy by affecting T cell activation.

摘要

食物过敏是一个主要的公共卫生问题。研究表明,抗原呈递细胞表面上的活化白细胞细胞黏附分子(ALCAM/CD166)与共刺激分子 CD6 之间的长期相互作用会影响免疫反应。然而,目前还没有关于 ALCAM 在食物过敏中的功能的研究。因此,我们旨在使用 ALCAM 缺陷小鼠鉴定 ALCAM 在卵清蛋白(OVA)诱导的食物过敏中的功能。野生型(WT)和 ALCAM 缺陷(ALCAM )小鼠经腹腔内和口服给予 OVA 致敏。杀死小鼠,分析与食物过敏和辅助性 T 细胞 2(Th2)免疫反应相关的参数。OVA 挑战的 WT 小鼠中 ALCAM 血清水平升高,mRNA 表达降低。OVA 挑战的 WT 小鼠血清免疫球蛋白(Ig)E 水平、Th2 细胞因子 mRNA 和组织学损伤均高于对照小鼠,而在 ALCAM 小鼠中则减弱。OVA 挑战的 ALCAM 小鼠的总细胞、CD3 CD4 T 细胞和活化 T 细胞的免疫组织 T 细胞增殖减少。抗 CD6 抗体降低了共培养的 T 细胞和树突状细胞(DC)的增殖。此外,用 OVA 脉冲的 ALCAM BM 来源的 DC 过继转移致敏的 WT 小鼠显示出免疫反应降低。最后,食物过敏儿童的血清 ALCAM 水平高于对照受试者。在这项研究中,食物过敏诱导的 WT 小鼠和食物过敏儿童的血清 ALCAM 水平升高。此外,OVA 挑战的 ALCAM 小鼠中的免疫反应和 T 细胞激活减弱。这些结果表明,ALCAM 通过影响 T 细胞激活来调节食物过敏。

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