Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Traditional Chinese Medicine, Guangzhou Eighth People's Hospital, Guangzhou, China.
Immunol Lett. 2021 Apr;232:39-44. doi: 10.1016/j.imlet.2021.02.001. Epub 2021 Feb 11.
Inflammatory bowel disease (IBD), consisting of ulcerative colitis (UC) and Crohn's disease (CD), is featured by overactive immune response and enduring course of unrestrained colitis. Genetic predisposition and environmental factors are fundamental in disease progression. Notably, microbiota dysregulation and its interaction with host mucosal barrier perplex disease phenotype. Under experimental setting, distinct mouse models are established to mimic human colitis process, including infection induced dysbiosis, dextran sulfate sodium (DSS) etc. induced barrier destruction, anti-CD40 L induced innate immunity dominant colitis and T cell transfer colitis model. Thus, from a more detailed aspect, IBD is heterogeneous and can be further classified into different subtypes based on the specific etiological pathways. As a typical inflammatory disorder, various immune cell types are involved in IBD pathogenesis. Among them, macrophages are believed to play a pivotal role. CX3CR1 macrophages, deriving from peripheral patrolling CD14 Ly6C monocytes, are specified cell population dwelling in the gut. Accumulating evidence suggests that CX3CR1 macrophages are critical for mucosal homeostasis and IBD pathogenesis, while some conflicts exist in current studies with both protective and harmful effects being revealed. Herein, we reviewed published literatures and found that the observed discrepancies stem from many aspects: the expression level of CX3CR1, the confounding dendritic cell subsets and most importantly, the different colitis stages and subtypes. Overall, CX3CR1 targeting strategy could be powerful weapon in fighting against colitis, but at the same time, the precise etiological and pathological mechanisms should be cautiously examined concerning the appropriate usage of CX3CR1 targeted therapy.
炎症性肠病（IBD）包括溃疡性结肠炎（UC）和克罗恩病（CD），其特征为过度活跃的免疫反应和持续的不受控制的结肠炎病程。遗传易感性和环境因素是疾病进展的基础。值得注意的是，微生物失调及其与宿主黏膜屏障的相互作用使疾病表型复杂化。在实验环境下，建立了不同的小鼠模型来模拟人类结肠炎过程，包括感染诱导的失调、葡聚糖硫酸钠（DSS）等诱导的屏障破坏、抗 CD40L 诱导的固有免疫主导性结肠炎和 T 细胞转移结肠炎模型。因此，从更详细的角度来看，IBD 是异质性的，可以根据特定的病因途径进一步分为不同的亚型。作为一种典型的炎症性疾病，各种免疫细胞类型参与 IBD 的发病机制。其中，巨噬细胞被认为发挥着关键作用。CX3CR1 巨噬细胞来源于外周巡逻的 CD14+Ly6C-单核细胞，是定殖于肠道的特定细胞群体。越来越多的证据表明，CX3CR1 巨噬细胞对于黏膜稳态和 IBD 的发病机制至关重要，而目前的研究中存在一些相互矛盾的结果，揭示了其既有保护作用又有有害作用。在此，我们回顾了已发表的文献，发现观察到的差异源于多个方面：CX3CR1 的表达水平、混杂的树突状细胞亚群，最重要的是，不同的结肠炎阶段和亚型。总的来说，针对 CX3CR1 的靶向策略可能是对抗结肠炎的有力武器，但同时，应该谨慎地检查其精确的病因和病理机制，以正确使用 CX3CR1 靶向治疗。
