粘膜免疫学的最新进展揭示了不同组织内细胞间连接的复杂网络，揭示了不同细胞类型的独特特性。这个复杂网络的核心是细胞因子 IL-33，它因其在各种疾病（从过敏到癌症、触发 2 型免疫反应等）中的关键作用而受到广泛关注。最近的研究挑战了先前将 IL-33 表达归因于上皮细胞的假设，强调基质细胞是脂肪组织和肺部的主要来源。然而，在复杂的肠道环境中，IL-33 在介导免疫监视和耐受性方面发挥着至关重要的作用，并与许多肠道相关疾病有关，其主要来源、调节和主要特征需要更多的探索。这项研究确定基质细胞是小肠中主要表达 IL-33 的细胞类型。通过研究它们的转录组和内在信号通路，我们发现了 IL-33 基质细胞在维持干细胞生态位中的可能作用以及它们与轴突发生调节相关神经元的潜在串扰。重要的是，我们的实验证明，原代肠基质细胞培养物的血管活性肠肽刺激可显着放大 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 IL-33 肠基质细胞在肠道中维持的大量相互作用的重大飞跃，为未来研究肠道基质神经串扰铺平了道路。这些发现为开发旨在利用 IL-33 在一系列疾病中的潜力的靶向治疗策略带来了巨大希望。版权所有 © 2024 Topczewska、Savvopoulou、Cosovanu 和 Klose。

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.Copyright © 2024 Topczewska, Savvopoulou, Cosovanu and Klose.