Laboratory of Immunobiology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
Laboratory of Immunobiology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
Semin Cell Dev Biol. 2019 Apr;88:138-146. doi: 10.1016/j.semcdb.2018.01.007. Epub 2018 Feb 1.
The gut is the biggest immune organ in the body that encloses commensal microbiota which aids in food digestion. Paneth cells, positioned at the frontline of host-microbiota interphase, can modulate the composition of microbiota. Paneth cells achieve this via the delivery of microbicidal substances, among which enteric α-defensins play the primary role. If microbiota is dysregulated, it can impact the function of the local mucosal immune system. Importantly, this system is also exposed to an enormous number of antigens which are derived from the gut-resident microbiota and processed food, and may potentially trigger undesirable local inflammatory responses. To understand the intricate regulations and liaisons between Paneth cells, microbiota and the immune system in this intestinal-specific setting, one must consider their mode of interaction in a wider context of regulatory processes which impose immune tolerance not only to self, but also to microbiota and food-derived antigens. These include, but are not limited to, tolerogenic mechanisms of central tolerance in the thymus and peripheral tolerance in the secondary lymphoid organs, and the intestine itself. Defects in these processes can compromise homeostasis in the intestinal mucosal immunity. In this review, which is focused on tolerance to intestinal antigens and its relevance for the pathogenesis of gut immune diseases, we provide an outline of such multilayered immune control mechanisms and highlight functional links that underpin their cooperative nature.
肠道是人体最大的免疫器官，其中包含共生微生物群，有助于食物消化。潘氏细胞位于宿主-微生物交界的前沿，可以调节微生物群的组成。潘氏细胞通过输送杀菌物质来实现这一点，其中肠型α-防御素起着主要作用。如果微生物群失调，它会影响局部黏膜免疫系统的功能。重要的是，这个系统还暴露于大量来自肠道常驻微生物群和加工食物的抗原，可能会引发不理想的局部炎症反应。为了理解肠道特有的潘氏细胞、微生物群和免疫系统之间的复杂调节和联系，必须考虑它们在免疫耐受的调节过程中的相互作用模式，这些过程不仅对自身，而且对微生物群和食物衍生抗原施加免疫耐受。其中包括但不限于胸腺中的中枢耐受和次级淋巴器官中的外周耐受，以及肠道本身。这些过程的缺陷会破坏肠道黏膜免疫的体内平衡。在这篇专注于肠道抗原耐受及其与肠道免疫疾病发病机制相关性的综述中，我们概述了这种多层次的免疫控制机制，并强调了支持其协同性质的功能联系。
