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IL-1 和 CD40/CD40L 血小板复合物:诱导克罗恩病的因素和新的治疗靶点。

IL-1 and CD40/CD40L platelet complex: elements of induction of Crohn's disease and new therapeutic targets.

机构信息

Department of Biology, Faculty of Sciences, Hassan II University, Casablanca, Morocco.

Laboratory of Genetic and Molecular Pathology, Faculty of Medicine, Hassan II University, Casablanca, Morocco.

出版信息

Arch Pharm Res. 2021 Jan;44(1):117-132. doi: 10.1007/s12272-020-01296-1. Epub 2021 Jan 4.

Abstract

Ulcerative colitis (UC) and Crohn's disease (CD) are chronic and multifactorial diseases that affect the intestinal tract, both characterized by recurrent inflammation of the intestinal mucosa, resulting in abdominal pain, diarrhea, vomiting and, rectal bleeding. Inflammatory bowel diseases (IBD) regroup these two disorders. The exact pathological mechanism of IBD remains ambiguous and poorly known. In genetically predisposed patients, defects in intestinal mucosal barrier are due to an uncontrolled inflammatory response to normal flora. In addition to the genetic predisposition, these defects could be triggered by environmental factors or by a specific lifestyle which is widely accepted as etiological hypothesis. The involvement of the CD40/CD40L platelet complex in the development of IBD has been overwhelmingly demonstrated. CD40L is climacteric in cell signalling in innate and adaptive immunity, the CD40L expression on the platelet cell surface gives them an immunological competence. The IL-1, a major inflammation mediator could be involved in different ways in the development of IBD. Here, we provide a comprehensive review regarding the role of platelet CD40/CD40L in the pathophysiological effect of IL-1 in the development of Crohn's disease (CD). This review could potentially help future approaches aiming to target these two pathways for therapeutic purposes and elucidate the immunological mechanisms driving gut inflammation.

摘要

溃疡性结肠炎(UC)和克罗恩病(CD)是影响肠道的慢性和多因素疾病,两者均以肠道黏膜的复发性炎症为特征,导致腹痛、腹泻、呕吐和直肠出血。炎症性肠病(IBD)将这两种疾病归为一组。IBD 的确切病理机制仍不清楚,知之甚少。在遗传易感患者中,肠黏膜屏障缺陷是由于对正常菌群的失控炎症反应。除了遗传易感性外,这些缺陷可能由环境因素或特定的生活方式触发,这被广泛接受为病因假说。CD40/CD40L 血小板复合物在 IBD 发展中的作用已得到充分证明。CD40L 在先天和适应性免疫中的细胞信号转导中起关键作用,血小板细胞表面的 CD40L 赋予它们免疫能力。IL-1 是一种主要的炎症介质,可能以不同的方式参与 IBD 的发展。在这里,我们提供了关于血小板 CD40/CD40L 在 IL-1 对克罗恩病(CD)发展的病理生理作用中的作用的全面综述。这一综述可能有助于未来针对这两个途径进行治疗的方法,并阐明驱动肠道炎症的免疫机制。

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