Human intestinal stromal cells promote homeostasis in normal mucosa but inflammation in Crohn’s disease in a retinoic acid–deficient manner

IF 7.9 2区 医学 Q1 IMMUNOLOGY
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引用次数: 0

Abstract

Intestinal stromal cells (SCs), which synthesize the extracellular matrix that gives the mucosa its structure, are newly appreciated to play a role in mucosal inflammation. Here, we show that human intestinal vimentin+CD90+smooth muscle actin SCs synthesize retinoic acid (RA) at levels equivalent to intestinal epithelial cells, a function in the human intestine previously attributed exclusively to epithelial cells. Crohn’s disease SCs (Crohn’s SCs), however, synthesized markedly less RA than SCs from healthy intestine (normal SCs). We also show that microbe-stimulated Crohn’s SCs, which are more inflammatory than stimulated normal SCs, induced less RA-regulated differentiation of mucosal dendritic cells (DCs) (circulating pre-DCs and monocyte-derived DCs), leading to the generation of more potent inflammatory interferon-γhi/interleukin-17hi T cells than normal SCs. Explaining these results, Crohn’s SCs expressed more DHRS3, a retinaldehyde reductase that inhibits retinol conversion to retinal and, thus, synthesized less RA than normal SCs. These findings uncover a microbe–SC–DC crosstalk in which luminal microbes induce Crohn’s disease SCs to initiate and perpetuate inflammation through impaired synthesis of RA.
人类肠道基质细胞以缺乏维甲酸的方式促进正常粘膜的稳态,但在克罗恩病中则促进炎症。
肠道基质细胞(SCs)合成细胞外基质,赋予粘膜结构,新近被认为在粘膜炎症中发挥作用。在这里,我们展示了人类肠道波形蛋白+CD90+SMA- SCs合成维甲酸(RA)的水平与肠道上皮细胞相当,而这种功能在人类肠道中以前被认为是上皮细胞的专有功能。然而,克罗恩病 SCs(克罗恩 SCs)合成的视黄酸明显少于健康肠道 SCs(正常 SCs)。我们还发现,微生物刺激的克罗恩病 SCs 比刺激的正常 SCs 具有更强的炎症性,它们诱导的由 RA 调节的粘膜 DCS(循环前 DCs 和单核细胞衍生 DCs)分化较少,从而产生了比正常 SCs 更强的炎症性 IFN-γhi/IL-17hi T 细胞。为了解释这些结果,克罗恩病 SCs 表达了更多的 DHRS3(一种抑制视黄醇转化为视黄醛的视黄醛还原酶),因此合成的 RA 比正常 SCs 少。这些发现揭示了微生物-SC-DC 之间的串联作用,其中管腔微生物诱导克罗恩病 SCs 通过受损的 RA 合成启动和延续炎症。
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
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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