Immune signaling mediates stromal changes to support epithelial reprogramming in celiac duodenum.

IF 6.9 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-07-21 DOI:10.1016/j.celrep.2025.116039

Dylan Richards, Klebea Sohn, Shrikanth Chomanahalli Basavarajappa, Daniel Horowitz, Joshua Rusbuldt, Lynn Tomsho, Kate Paget, Ivan Chavez, Koen Van den Berge, Brad McRae, Heather Loughnane, Seamus Hussey, Patrick Walsh, Darren Ruane

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引用次数: 0

Abstract

Celiac disease is a chronic autoimmune disorder affecting 0.5%-1% of the population. Here, we assembled the most comprehensive single-cell RNA sequencing (scRNA-seq) dataset in celiac disease (CeD) to date, including 203,555 cells across 21 active CeD and 11 control duodenal samples. CeD was characterized by single-cell differential changes in abundance, gene expression, and cell-cell interactions across cellular compartments versus control. Epithelial changes included increased stem/crypt and secretory epithelial cells in CeD and decreased absorptive enterocytes, reflecting crypt hyperplasia and villus atrophy. Distinct changes in stromal populations correlated with epithelial changes, particularly increased abundance and transcriptional activity of NRG1 and SMOC2 fibroblasts. Cell-cell interaction analysis proposed a distinct increased role of fibroblasts to support epithelial reprogramming of the increased stem/crypt epithelial fraction in CeD, mediated by myeloid derived interleukin-1β (IL-1β) and lymphoid-derived interferon γ (IFN-γ). This dataset reveals a role for T-myeloid-stromal-epithelial cell communication in CeD, highlighting key mechanisms of the tissue-level cellular dynamics in response to gluten ingestion.

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免疫信号介导间质改变以支持腹腔十二指肠上皮重编程。

乳糜泻是一种慢性自身免疫性疾病，影响0.5%-1%的人口。在这里，我们收集了迄今为止最全面的乳糜泻（CeD）单细胞RNA测序（scRNA-seq）数据集，包括21个活性CeD和11个对照十二指肠样本的203,555个细胞。CeD的特征是单细胞在丰度、基因表达和细胞间相互作用方面的差异变化。上皮变化包括CeD中干/隐窝和分泌性上皮细胞增加，吸收性肠细胞减少，反映隐窝增生和绒毛萎缩。基质群体的明显变化与上皮细胞的变化相关，特别是NRG1和SMOC2成纤维细胞的丰度和转录活性增加。细胞-细胞相互作用分析表明，在髓源性白细胞介素-1β (IL-1β)和淋巴源性干扰素γ (IFN-γ)介导下，成纤维细胞在支持CeD中增加的干/隐上皮部分的上皮重编程中的作用明显增强。该数据集揭示了t -骨髓-基质-上皮细胞通讯在CeD中的作用，突出了组织水平细胞动力学响应谷蛋白摄入的关键机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.