转录分析将表达IL-33的肠道基质细胞鉴定为有助于与肠神经元相互作用的信号中心
Transcriptional profiling identifies IL-33-expressing intestinal stromal cells as a signaling hub poised to interact with enteric neurons
影响因子:4.30000
分区:生物学2区 / 发育生物学2区 细胞生物学3区
发表日期:2024
作者:
Patrycja M Topczewska, Anna Savvopoulou, Catalina Cosovanu, Christoph S N Klose
摘要
粘膜免疫学方面的最新进展已公布了各种组织中复杂的细胞间连接网络，从而阐明了不同细胞类型的独特特性。这个复杂的网络的核心是细胞因子IL-33，它因其在从过敏到癌症的各种疾病中的关键作用而引起了极大的关注，触发了2型免疫反应等。最近的研究挑战了先前的假设，将IL-33表达归因于上皮细胞，突出了基质细胞作为脂肪组织和肺部主要来源。但是，在肠道的复杂景观中，IL-33在介导免疫监测和耐受性中起着至关重要的作用，并且与许多与肠道有关的疾病有关，其主要来源，调节和主要特征需要更多的探索。这项研究将基质细胞鉴定为小肠中的主要表达IL-33细胞类型。通过研究其转录组和固有信号通路，我们发现了IL-33+基质细胞在维持干细胞生态位及其与轴突生成有关的神经元的潜在串扰中的可能作用。重要的是，我们的实验表明，原发性肠道基质细胞培养的血管活性肠肽刺激显着放大了mRNA和蛋白质水平上的IL-33表达。因此，我们的研究代表了理解大量相互作用IL-33+肠道基质细胞维持在肠道中的重大飞跃，这为未来对肠道中基质 - Neuro Crosstalk的研究铺平了道路。这些发现对开发旨在利用跨疾病范围内IL-33的潜力的有针对性的治疗策略具有巨大的希望。
Abstract
Recent advancements in mucosal immunology have unveiled a complex network of intercellular connections within diverse tissues, shedding light on the unique properties of different cell types. Central to this intricate network is the cytokine IL-33, which has gained significant attention for its critical role in various diseases, from allergy to cancer, triggering type 2 immune responses, among others. Recent research has challenged the prior assumptions attributing IL-33 expression to epithelial cells, highlighting stromal cells as the predominant source in adipose tissue and the lungs. However, in the complex landscape of the intestine, where IL-33 plays a crucial role in mediating immune surveillance and tolerance and is implicated in many gut-related disorders, its primary source, regulation, and main characteristics need more exploration. This study identifies stromal cells as the primary IL-33-expressing cell type in the small intestine. By investigating their transcriptome and intrinsic signaling pathways, we have uncovered a possible role of IL-33+ stromal cells in maintaining the stem cell niche and their potential crosstalk with neurons relevant to the regulation of axonogenesis. Importantly, our experiments have demonstrated that vasoactive intestinal peptide stimulation of a primary intestinal stromal cell culture significantly amplifies IL-33 expression on mRNA and protein level. Therefore, our study represents a significant leap forward in understanding the plethora of interactions IL-33+ intestinal stromal cells maintain in the intestine, paving the way for future investigations into stromal-neuro crosstalk in the gut. These findings hold great promise for developing targeted therapeutic strategies aimed at harnessing the potential of IL-33 across a spectrum of diseases.