Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon.
Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon.
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DOI：
10.1371/journal.ppat.1002714
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Takeda K
中科院分区：
文献类型：
--
作者：
Jeon SG;Kayama H;Ueda Y;Takahashi T;Asahara T;Tsuji H;Tsuji NM;Kiyono H;Ma JS;Kusu T;Okumura R;Hara H;Yoshida H;Yamamoto M;Nomoto K;Takeda K
特定的肠道微生物群已显示诱导Foxp 3+调节性T细胞发育。然而，目前还不清楚另一种调节性T细胞亚群Tr 1细胞的发育在肠道中是如何调节的。在这里，我们分析了肠道细菌的两种益生菌菌株，干酪乳杆菌和短双歧杆菌在肠道T细胞发育中的作用。B。breve，而不是L. casei诱导大肠中表达cMaf、IL-21和Ahr的产生IL-10的Tr 1细胞的发育。肠道CD 103+树突状细胞（DC）介导的B。breve诱导产生IL-10的T细胞的发育。来自Il 10 −/−、Tlr 2 −/−和Myd 88 −/−小鼠的CD 103 + DC显示缺陷的B。breve诱导的Tr 1细胞发育。B。breve处理的CD 103 + DCs不能诱导共培养的IL-10产生。B。对Tlr 2 −/−小鼠的短暂治疗没有增加结肠固有层中产生IL-10的T细胞。因此，B。breve通过TLR 2/MyD 88途径激活肠道CD 103 + DCs产生IL-10和IL-27，从而诱导大肠中产生IL-10的Tr 1细胞。口服B。短期给药改善了免疫功能低下小鼠的结肠炎，这些小鼠接受了来自野生型小鼠的幼稚CD 4 + T细胞，但对Il 10 −/−小鼠无效。这些结果表明，B。breve通过诱导肠道产生IL-10的Tr 1细胞来预防肠道炎症。与Foxp 3+调节性T细胞发育的诱导不同，目前尚不清楚肠道环境因素如何调节另一种调节性T细胞亚群（产生IL-10的Tr 1细胞）的发育。在这项研究中，我们揭示了益生菌菌株，短双歧杆菌诱导IL-10产生Tr 1细胞，表达c-Maf，IL-21，和Ahr通过激活肠道CD 103 + DC在大肠。使用几个基因靶向小鼠，我们表明，B。Breve诱导的产生IL-10的Tr 1细胞的发育依赖于DC通过TLR 2/MyD 88途径分泌IL-10和27。我们最终证明了B。Breve通过T细胞产生IL-10改善免疫功能低下小鼠的T细胞依赖性结肠炎。这些结果表明，B。Breve通过诱导肠道产生IL-10的Tr 1细胞来维持肠道稳态。
Specific intestinal microbiota has been shown to induce Foxp3+ regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103+ dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103+ DCs from Il10 −/−, Tlr2 −/−, and Myd88 −/− mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103+ DCs failed to induce IL-10 production from co-cultured Il27ra −/− T cells. B. breve treatment of Tlr2 −/− mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103+ DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4+ T cells from wild-type mice, but not Il10 −/− mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells. Unlike induction of Foxp3+ regulatory T cell development, it remains unclear how intestinal environmental factors regulate development of another regulatory T cell subset, Tr1 cells that produce IL-10. In this study, we reveal that a probiotic strain, Bifidobacterium breve induces IL-10-producing Tr1 cells that express c-Maf, IL-21, and Ahr via activation of intestinal CD103+ DCs in the large intestine. Using several gene-targeted mice, we show that B. breve-induced development of IL-10-producing Tr1 cells is dependent on DC secretion of IL-10 and 27 via a TLR2/MyD88 pathway. We finally show that B. breve ameliorated T cell-dependent colitis in immunocompromised mice via T cell production of IL-10. These findings demonstrate that B. breve maintains intestinal homeostasis through the induction of intestinal IL-10-producing Tr1 cells.
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影响因子：
2.7
作者：
HABU, Y;NAGAOKA, M;AZUMA, I
通讯作者：
AZUMA, 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：
64.8
作者：
Fukuda, Shinji;Toh, Hidehiro;Ohno, Hiroshi
通讯作者：
Ohno, Hiroshi
影响因子：
4.4
作者：
Kaji, Rumi;Kiyoshima-Shibata, Junko;Shida, Kan
通讯作者：
Shida, Kan
影响因子：
64.5
作者：
Elinav E;Strowig T;Kau AL;Henao-Mejia J;Thaiss CA;Booth CJ;Peaper DR;Bertin J;Eisenbarth SC;Gordon JI;Flavell RA
通讯作者：
Flavell RA