转录组分析发现，表达IL-33的肠道基质细胞是与肠神经元潜在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
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影响因子:4.3
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
DOI:
10.3389/fcell.2024.1420313
摘要
黏膜免疫学的最新进展揭示了多样组织内细胞间复杂的连接网络，阐明了不同细胞类型的独特特性。核心于这一复杂网络的关键细胞因子是IL-33，它在多种疾病中扮演重要角色，从过敏到癌症，能引发2型免疫反应等。近期研究挑战了以前认为IL-33主要由上皮细胞产生的假设，强调在脂肪组织和肺中，间质细胞是主要来源。然而，在肠道这一复杂环境中，IL-33在介导免疫监视和耐受中起关键作用，且与多种肠道疾病相关，其主要来源、调控机制和特征仍需进一步探索。本研究确认间质细胞为小肠中IL-33的主要表达细胞。通过分析其转录组及内在信号通路，发现IL-33+间质细胞可能在维持干细胞微环境和与神经元的潜在交流中发挥作用，尤其与轴突发生调控有关。重要的是，我们的实验显示，肠道血管活性肠肽（VIP）刺激原代肠道间质细胞，显著增强IL-33的mRNA和蛋白表达。因此，本研究在理解IL-33+肠道间质细胞在肠道中的多重作用方面迈出了重要一步，为未来研究肠道中间质-神经元的交互提供基础。这些发现为开发针对多种疾病的IL-33靶向治疗策略提供了巨大潜力。
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.