Control of Gut Inflammation by Modulation of Purinergic Signaling.
Control of Gut Inflammation by Modulation of Purinergic Signaling.
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DOI：
10.3389/fimmu.2020.01882
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发表时间：
2020
影响因子：
7.3
通讯作者：
Longhi MS
中科院分区：
文献类型：
--
作者：
Vuerich M;Mukherjee S;Robson SC;Longhi MS
炎症性肠病（IBD）是一种严重的胃肠道炎症。克罗恩病（CD）和溃疡性结肠炎（UC）是两种最常见的IBD表现，都与无限制的炎症有关，通常对传统的免疫抑制治疗难以治愈。在这两种情况下，效应和调节细胞免疫反应之间的不平衡已被记录，并被认为有助于疾病的发病机制。嘌呤能信号是一种已知的全身和局部炎症的调节剂，越来越多的证据表明，细胞外ATP/腺苷失衡是ibd相关免疫失调的关键决定因素。体外和临床前研究表明，ATP （P2）和腺苷（P1）受体在决定疾病的发病和严重程度方面都起作用。此外，我们的实验数据表明，ENTPD1/CD39和CD73外切酶是肠道炎症的关键调节剂，具有明确的翻译重要性。在这里，我们将提供关于嘌呤能信号在IBD中调节免疫反应中的作用的最新知识概述。我们还将回顾和讨论支持使用嘌呤能疗法纠正CD和UC中免疫失调的最有希望的发现。
Inflammatory bowel disease (IBD) is a serious inflammatory condition of the gastrointestinal tract. Crohn's disease (CD) and ulcerative colitis (UC) are two of the most common IBD manifestations and are both associated with unfettered inflammation, often refractory to conventional immunosuppressive treatment. In both conditions, imbalance between effector and regulatory cell immune responses has been documented and is thought to contribute to disease pathogenesis. Purinergic signaling is a known modulator of systemic and local inflammation and growing evidences point to extracellular ATP/adenosine imbalance as a key determinant factor in IBD-associated immune dysregulation. In vitro and pre-clinical studies suggest a role for both ATP (P2) and adenosine (P1) receptors in dictating onset and severity of the disease. Moreover, our experimental data indicate ENTPD1/CD39 and CD73 ectoenzymes as pivotal modulators of intestinal inflammation, with clear translational importance. Here we will provide an updated overview of the current knowledge on the role of the purinergic signaling in modulating immune responses in IBD. We will also review and discuss the most promising findings supporting the use of purinergic-based therapies to correct immune dysregulation in CD and UC.
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