Mineralocorticoid receptor deficiency in Treg cells ameliorates DSS‐induced colitis in a gut microbiota‐dependent manner
Mineralocorticoid receptor deficiency in Treg cells ameliorates DSS‐induced colitis in a gut microbiota‐dependent manner
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Treg 细胞中盐皮质激素受体缺乏可通过肠道微生物群依赖性方式改善 DSS 诱导的结肠炎
DOI：
10.1111/imm.13522
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发表时间：
2022-06
期刊：
影响因子：
6.4
通讯作者：
Sheng-Zhong Duan
中科院分区：
文献类型：
--
作者：
Ting Liu;Yu-Lin Li;Lu-Jun Zhou;Xue-Nan Sun;Yong-Li Wang;Lin-Juan Du;Yuan Liu;Hong Zhu;Bo-Yan Chen;Jian-Yong Sun;Yan Liu;Shuo Xu;Hui-Lin Ye;Shi-Jia Huang;Xiaoxia Wang;Bin Li;Sheng-Zhong Duan
盐皮质激素受体(MR)是一种经典的核受体，也是心血管系统的有效药物靶点。MR在巨噬细胞和T细胞等免疫细胞中的作用日益受到重视。本研究旨在探讨Treg MR在炎症性肠病(IBD)发病过程中的作用。我们用葡聚糖硫酸钠治疗Treg MR缺陷小鼠(MRflx/Foxp3YFP-Cre，KO)和对照组(Foxp3YFP-Cre，WT)诱导结肠炎，发现DSS诱导的小鼠结肠炎的严重程度明显减轻，并伴有炎性细胞因子的产生减少，单核细胞、中性粒细胞和干扰素γ+T细胞在结肠固有层的浸润减少。用16S rRNA基因测序分析了结肠炎小鼠的粪便微生物区系，发现Treg MR缺陷小鼠肠道微生物区系的组成发生了很大的变化。此外，抗生素耗尽肠道微生物群取消了Treg MR缺乏的保护作用，并导致了WT和KO小鼠DSS诱导的结肠炎的相似严重程度。与WT小鼠相比，来自KO小鼠的粪便微生物群移植减轻了DSS诱导的结肠炎，其特征是减轻了炎症渗透。因此，我们的研究表明，Treg MR缺陷通过减轻结肠炎性浸润来保护DSS诱导的结肠炎。肠道微生物区系是Treg MR缺乏症发挥有益作用的充分和必要条件。
Mineralocorticoid receptor (MR) is a classic nuclear receptor and an effective drug target in the cardiovascular system. The function of MR in immune cells such as macrophages and T cells has been increasingly appreciated. The aim of this study was to investigate the function of Treg MR in the process of inflammatory bowel disease (IBD). We treated Treg MR-deficient (MRflox/floxFoxp3YFP-Cre, KO) mice and control (Foxp3YFP-Cre, WT) mice with dextran sodium sulphate (DSS) to induce colitis and found that the severity of DSS-induced colitis was markedly alleviated in Treg MR-deficient mice, accompanied by reduced production of inflammatory cytokines, and relieved infiltration of monocytes, neutrophils and interferon γ+ T cells in colon lamina propria. Fecal microbiota of mice with colitis was analyzed by 16S rRNA gene sequencing and the composition of gut microbiota was vastly changed in Treg MR-deficient mice. Furthermore, depletion of gut microbiota by antibiotics abolished the protective effects of Treg MR deficiency and resulted in similar severity of DSS-induced colitis in WT and KO mice. Fecal microbiota transplantation from KO mice attenuated DSS-induced colitis characterized by alleviated inflammatory infiltration compared to that from WT mice. Hence, our study demonstrates that Treg MR deficiency protects against DSS-induced colitis by attenuation of colonic inflammatory infiltration. Gut microbiota is both sufficient and necessary for Treg MR deficiency to exert the beneficial effects.
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影响因子：
20.1
作者：
Ferrario CM;Schiffrin EL
通讯作者：
Schiffrin EL
影响因子：
4.5
作者：
Yasuma T;Toda M;Abdel-Hamid AM;D'Alessandro-Gabazza C;Kobayashi T;Nishihama K;D'Alessandro VF;Pereira GV;Mackie RI;Gabazza EC;Cann I
通讯作者：
Cann I
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
17.1
作者：
Khan, Shahanshah;Waliullah, Sumyya;Zaki, Hasan
通讯作者：
Zaki, Hasan
影响因子：
12.2
作者：
Zafar H;Saier MH Jr
通讯作者：
Saier MH Jr