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Natural killer T cells mediate inflammation in the bile ducts.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2018-11-01 , DOI: 10.1038/s41385-018-0066-8
N L Berntsen 1, 2 , B Fosby 1, 3 , C Tan 1 , H M Reims 4 , J Ogaard 2 , X Jiang 1, 2 , E Schrumpf 1, 2 , L Valestrand 1, 2 , T H Karlsen 1, 2, 5, 6 , P-D Line 3, 6 , R S Blumberg 7 , E Melum 1, 2, 5, 6
Affiliation  

Cholangiocytes function as antigen-presenting cells with CD1d-dependent activation of natural killer T (NKT) cells in vitro. NKT cells may act both pro- and anti-inflammatory in liver immunopathology. We explored this immune pathway and the antigen-presenting potential of NKT cells in the bile ducts by challenging wild-type and Cd1d-/- mice with intrabiliary injection of the NKT cell activating agent oxazolone. Pharmacological blocking of CD1d-mediated activation was performed with a monoclonal antibody. Intrabiliary oxazolone injection in wild-type mice caused acute cholangitis with significant weight loss, elevated serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin, increased histologic grade of cholangitis and number of T cells, macrophages, neutrophils and myofibroblasts per portal tract after 7 days. NKT cells were activated after intrabiliary injection of oxazolone with upregulation of activation markers. Cd1d-/- and wild-type mice pretreated with antibody blocking of CD1d were protected from disease. These findings implicate that cells in the bile ducts function as antigen-presenting cells in vivo and activate NKT cells in a CD1d-restricted manner. The elucidation of this biliary immune pathway opens up for potentially new therapeutic approaches for cholangiopathies.

中文翻译:

自然杀伤 T 细胞介导胆管炎症。

胆管细胞作为抗原呈递细胞发挥作用,在体外具有 CD1d 依赖性自然杀伤 T (NKT) 细胞激活。NKT 细胞可能在肝脏免疫病理学中起到促炎和抗炎作用。我们通过挑战野生型和 Cd1d -/-探索了这种免疫途径和胆管中 NKT 细胞的抗原呈递潜力给小鼠胆内注射 NKT 细胞活化剂恶唑酮。用单克隆抗体对 CD1d 介导的激活进行药理学阻断。野生型小鼠胆内注射恶唑酮引起急性胆管炎,体重显着下降,丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶和胆红素的血清水平升高,胆管炎的组织学分级增加,每个门道的 T 细胞、巨噬细胞、中性粒细胞和肌成纤维细胞数量增加7天后。NKT 细胞在胆内注射恶唑酮后被激活,激活标记上调。Cd1d -/-用抗体阻断 CD1d 预处理的野生型小鼠免受疾病侵害。这些发现暗示胆管中的细胞在体内充当抗原呈递细胞并以 CD1d 限制的方式激活 NKT 细胞。这种胆道免疫通路的阐明为胆管病的潜在新治疗方法开辟了道路。
更新日期:2018-08-17
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