Retinoid Signaling in Intestinal Epithelial Cells Is Essential for Early Survival From Gastrointestinal Infection.
Retinoid Signaling in Intestinal Epithelial Cells Is Essential for Early Survival From Gastrointestinal Infection.
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DOI：
10.3389/fimmu.2020.559635
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发表时间：
2020
影响因子：
7.3
通讯作者：
Cantorna MT
中科院分区：
文献类型：
--
作者：
Snyder LM;Arora J;Kennett MJ;Weaver V;Cantorna MT
维生素A缺乏（A-）增加胃肠道（GI）感染的发病率和死亡率。阻断肠上皮细胞（IEC，IECdnRAR）中的类维生素A信号传导（显性负性视黄酸受体，dnRAR）对维生素A的吸收，紧密连接蛋白的表达或屏障的完整性没有影响。在IECdnRAR小鼠中，肠道中的免疫细胞以正常频率存在，但T细胞受体（TCR）αβ+/CD 8 αα细胞除外，其显著低于野生型同窝小鼠。用葡聚糖硫酸钠接种IECdnRAR小鼠以诱导结肠炎或啮齿类柠檬酸杆菌感染，导致与野生型同窝出生小鼠相似的疾病。给小鼠喂食缺乏维生素A的饮食会降低维生素A的状态，A-IECdnRAR小鼠会发展成更严重的结肠炎和C。啮齿类感染特别是，类维生素A信号在IEC是至关重要的A-宿主生存的早期感染后，C。啮齿动物。在感染当天开始用视黄酸（RA）治疗A-小鼠保护大多数小鼠免于早期致死。然而，RA治疗A-IECdnRAR小鼠对于预防C.啮齿类感染IEC中的Retionid信号传导至关重要，特别是当膳食维生素A水平降低时。IEC是维生素A的直接靶点，用于建立对感染的早期防御。
Vitamin A deficiency (A–) increases morbidity and mortality to gastrointestinal (GI) infection. Blocking retinoid signaling (dominant negative retinoic acid receptor, dnRAR) in intestinal epithelial cells (IEC, IECdnRAR) had no effect on vitamin A absorption, the expression of tight junction proteins or the integrity of the barrier. Immune cells in the gut were present in normal frequencies in the IECdnRAR mice, with the exception of the T cell receptor (TCR)αβ+/CD8αα cells, which were significantly lower than in wildtype littermates. Challenging the IECdnRAR mice with dextran sodium sulfate to induce colitis or Citrobacter rodentium infection resulted in similar disease to wildtype littermates. Feeding mice vitamin A deficient diets reduced vitamin A status and the A– IECdnRAR mice developed more severe colitis and C. rodentium infection. In particular, retinoid signaling in the IEC was crucial for the A– host to survive early infection following C. rodentium. Treating A– mice with retinoic acid (RA) beginning on the day of infection protects most mice from early lethality. However, RA treatment of the A– IECdnRAR mice was ineffective for preventing lethality following C. rodentium infection. Retionid signaling in IEC is critical, especially when there are reduced levels of dietary vitamin A. IEC are direct targets of vitamin A for mounting early defense against infection.
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DOI：
10.4049/jimmunol.0900420
发表时间：
2009-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ma LJ;Acero LF;Zal T;Schluns KS
通讯作者：
Schluns KS
影响因子：
3.1
作者：
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影响因子：
3.7
作者：
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DOI：
10.1073/pnas.90.7.2989
发表时间：
1993-04-01
影响因子：
11.1
作者：
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通讯作者：
EVANS, RM
DOI：
10.1073/pnas.0831037100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Das, G;Augustine, MM;Ray, A
通讯作者：
Ray, A