Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, Glasgow, UK.
Immunology. 2020 Aug;160(4):313-324. doi: 10.1111/imm.13191. Epub 2020 Apr 20.
The intestine is continuously exposed to an enormous variety and quantity of antigens and innate immune stimuli derived from both pathogens and harmless materials, such as food and commensal bacteria. Accordingly, the intestinal immune system is uniquely adapted to ensure appropriate responses to the different kinds of challenge; maintaining tolerance to harmless antigens in the steady-state, whilst remaining poised to deal with potential pathogens. To accomplish this, leucocytes of the intestinal immune system have to adapt to a constantly changing environment and interact with many different non-leucocytic intestinal cell types, including epithelial and endothelial cells, neurons, and a heterogenous network of intestinal mesenchymal cells (iMC). These interactions are intricately involved in the generation of protective immunity, the elaboration of inflammatory responses, and the development of inflammatory conditions, such as inflammatory bowel diseases. Here we discuss recent insights into the immunological functions of iMC under homeostatic and inflammatory conditions, focusing particularly on iMC in the mucosa and submucosa, and highlighting how an appreciation of the immunology of iMC may help understand the pathogenesis and treatment of disease.
肠道不断暴露于大量不同的抗原和先天免疫刺激物中,这些刺激物来源于病原体和无害物质,如食物和共生细菌。因此,肠道免疫系统经过了独特的适应,以确保对不同种类的挑战做出适当的反应;在稳态下对无害抗原保持耐受,同时准备应对潜在的病原体。为了实现这一目标,肠道免疫系统的白细胞必须适应不断变化的环境,并与许多不同的非白细胞肠道细胞类型相互作用,包括上皮细胞和内皮细胞、神经元以及异质的肠道间充质细胞网络(iMC)。这些相互作用错综复杂地涉及保护性免疫的产生、炎症反应的阐明以及炎症性疾病的发展,如炎症性肠病。在这里,我们讨论了在稳态和炎症条件下 iMC 的免疫功能的最新见解,特别关注黏膜和黏膜下层中的 iMC,并强调了对 iMC 免疫学的认识如何有助于理解疾病的发病机制和治疗。