CD8+ T Cells Contribute to the Development of Coronary Arteritis in the Lactobacillus casei Cell Wall Extract-Induced Murine Model of Kawasaki Disease.
CD8+ T Cells Contribute to the Development of Coronary Arteritis in the Lactobacillus casei Cell Wall Extract-Induced Murine Model of Kawasaki Disease.
复制标题
CD8+ T细胞有助于乳酸杆菌壳细胞壁提取物诱导的川崎疾病的鼠模型的冠状动脉炎的发展。
DOI：
10.1002/art.39939
复制
发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Arditi M
中科院分区：
文献类型：
--
作者：
Noval Rivas M;Lee Y;Wakita D;Chiba N;Dagvadorj J;Shimada K;Chen S;Fishbein MC;Lehman TJ;Crother TR;Arditi M
川崎（KD）是发达国家儿童获得性心脏病的主要病因。人KD冠状动脉病变的特征在于浸润性CD3+ T细胞的存在增加，然而不同T细胞亚群在冠状动脉炎发展中的具体贡献仍然未知。因此，我们试图研究CD 4+、CD 8+、调节性T细胞（TReg）和NK T细胞在KD发病机制中的功能。通过使用干酪乳杆菌细胞壁提取物（LCWE）诱导的KD血管炎的良好建立的小鼠模型来解决KD发展中的T细胞亚群功能。注射LCWE的小鼠出现冠状动脉病变，其特征在于存在炎性细胞浸润。通常，这种慢性炎症会导致冠状动脉完全闭塞，原因是管腔肌成纤维细胞增殖（LMP）以及冠状动脉炎和冠状动脉炎的发展。在这项研究中，我们通过使用几种敲除（KO）小鼠品系和耗竭单克隆抗体，证明了KD血管炎发展中对CD8+ T细胞的需求，而不是CD4+、NK T细胞或TReg细胞。LCWE诱导的KD血管炎小鼠模型模拟了人类疾病的许多组织学特征，例如冠状动脉病变中存在CD 8 + T细胞和LMP以及心外膜冠状动脉炎。此外，在该KD鼠模型中，CD8+ T细胞在功能上有助于KD血管炎的发展。靶向浸润性CD8+ T细胞的治疗策略可能有助于人类KD的管理。
Kawasaki disease (KD) is the leading cause of acquired heart disease among children in developed countries. Human KD coronary lesions are characterized by increased presence of infiltrating CD3+ T cells, however the specific contributions of the different T cell subpopulations in coronary arteritis development remains unknown. Therefore, we sought to investigate the function of CD4+, CD8+, Regulatory T cells (TReg), and NK T cells in the pathogenesis of the KD. T cell subsets function in KD development was addressed by using a well-established murine model of Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis. LCWE-injected mice developed coronary lesions characterized by the presence of inflammatory cell infiltrations. Frequently, this chronic inflammation resulted in complete occlusion of the coronaries due to luminal myofibroblast proliferation (LMP) as well as the development of coronary arteritis and aortitis. In this study we demonstrate the requirement of CD8+ T cells but not CD4+, NK T cells or TReg cells in the development of KD vasculitis by using several Knockout (KO) murine strains and depleting monoclonal antibodies. The LCWE-induced KD vasculitis murine model mimics many histological features of the human disease such as the presence of CD8+ T cells and LMP in the coronary artery lesions as well as epicardial coronary arteritis. Moreover, CD8+ T cells functionally contribute to the development of KD vasculitis in this KD murine model. Therapeutic strategies targeting infiltrating CD8+ T cells might be useful in the management of human KD.
川崎病中CD4CD25FOXP3 T细胞水平的改变。
影响因子：
--
作者：
Sohn SY;Song YW;Yeo YK;Kim YK;Jang GY;Woo CW;Lee JH;Lee KC
通讯作者：
Lee KC