Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity
Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity
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DOI：
10.1152/ajpgi.00114.2016
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发表时间：
2016-11-01
影响因子：
4.5
通讯作者：
de Jonge, Wouter J.
中科院分区：
文献类型：
--
作者：
Dhawan, Shobhit;De Palma, Giada;de Jonge, Wouter J.
胆碱能抗炎途径通过脾脏中产生乙酰胆碱的记忆T细胞减少全身性肿瘤坏死因子（TNF）。这些表达胆碱乙酰转移酶（ChAT）的T细胞也存在于肠道中，其功能尚不清楚。我们的目的是表征小鼠和人类肠道中的这些细胞，并描述它们的功能。我们利用ChAT增强的绿色荧光蛋白（eGFP）报告小鼠。将CD 4（Cre）小鼠与ChAT（fl/fl）小鼠杂交以实现CD 4（+）T细胞中ChAT的特异性缺失。我们观察到人和小鼠肠道中大多数ChAT表达T细胞具有Th 17细胞的特征，并共表达IL 17 A，IL 22和RORC。表达ChAT的T细胞的产生在其肾上腺素能受体β 2激活后被树突状细胞扭曲。为了评估ChAT T细胞功能，我们产生了CD 4特异性ChAT缺陷小鼠。CD 4ChAT（-/-）小鼠表现出上皮抗菌肽溶菌酶、防御素A和ang 4水平降低，这与CD 4ChAT（-/-）小鼠小肠腔中细菌多样性和丰富性增强有关。我们的结论是ChAT表达T细胞在肠道刺激肾上腺素能受体活化树突状细胞。表达ChAT的T细胞可能起介导宿主AMP分泌、微生物生长和扩增的作用。
The cholinergic anti-inflammatory pathway reduces systemic tumor necrosis factor (TNF) via acetylcholine-producing memory T cells in the spleen. These choline acetyltransferase (ChAT)-expressing T cells are also found in the intestine, where their function is unclear. We aimed to characterize these cells in mouse and human intestine and delineate their function. We made use of the ChAT-enhanced green fluorescent protein (eGFP) reporter mice. CD4(Cre) mice were crossed to ChAT(fl/fl) mice to achieve specific deletion of ChAT in CD4(+) T cells. We observed that the majority of ChAT-expressing T cells in the human and mouse intestine have characteristics of Th17 cells and coexpress IL17A, IL22, and RORC. The generation of ChAT-expressing T cells was skewed by dendritic cells after activation of their adrenergic receptor beta(2). To evaluate ChAT T cell function, we generated CD4-specific ChAT-deficient mice. CD4ChAT(-/-) mice showed a reduced level of epithelial antimicrobial peptides lysozyme, defensin A, and ang4, which was associated with an enhanced bacterial diversity and richness in the small intestinal lumen in CD4ChAT(-/-) mice. We conclude that ChAT-expressing T cells in the gut are stimulated by adrenergic receptor activation on dendritic cells. ChAT-expressing T cells may function to mediate the host AMP secretion, microbial growth and expansion.