CD1d-mediated lipid presentation by CD11c(+) cells regulates intestinal homeostasis.
CD1d-mediated lipid presentation by CD11c(+) cells regulates intestinal homeostasis.
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DOI：
10.15252/embj.201797537
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发表时间：
2018-03-01
期刊：
影响因子：
--
通讯作者：
Barral P
中科院分区：
文献类型：
--
作者：
Sáez de Guinoa J;Jimeno R;Gaya M;Kipling D;Garzón MJ;Dunn-Walters D;Ubeda C;Barral P
肠道内环境的稳定依赖于共生细菌和免疫系统之间的持续对话。自然杀伤T(NKT)细胞识别CD1d限制性微生物脂类和自身脂类，有助于调节粘膜免疫，但其功能机制尚不清楚。在这里，我们证明了NKT细胞对肠道脂质的反应和CD11c+细胞(包括树突状细胞(DC)和巨噬细胞)在介导肠道内的脂质递送，最终控制肠道NKT细胞的动态平衡和激活方面是必不可少的。相反，CD1d和NKT细胞参与控制肠道细菌的组成和区划，调节IgA谱系，并在肠道内诱导调节性T细胞。肠道动态平衡的这些变化需要DC/巨噬细胞表达CD1d，因为CD11c+细胞上CD1d有条件缺失的小鼠表现出生物失调和免疫动态平衡改变。这些结果揭示了CD11c+细胞在控制肠道间室脂类依赖性免疫中的重要性，并揭示了NKT细胞-DC串扰是调节肠道内稳态的关键机制。
Intestinal homeostasis relies on a continuous dialogue between the commensal bacteria and the immune system. Natural killer T (NKT) cells, which recognize CD1d‐restricted microbial lipids and self‐lipids, contribute to the regulation of mucosal immunity, yet the mechanisms underlying their functions remain poorly understood. Here, we demonstrate that NKT cells respond to intestinal lipids and CD11c+ cells (including dendritic cells (DCs) and macrophages) are essential to mediate lipid presentation within the gut ultimately controlling intestinal NKT cell homeostasis and activation. Conversely, CD1d and NKT cells participate in the control of the intestinal bacteria composition and compartmentalization, in the regulation of the IgA repertoire and in the induction of regulatory T cells within the gut. These changes in intestinal homeostasis require CD1d expression on DC/macrophage populations as mice with conditional deletion of CD1d on CD11c+ cells exhibit dysbiosis and altered immune homeostasis. These results unveil the importance of CD11c+ cells in controlling lipid‐dependent immunity in the intestinal compartment and reveal an NKT cell–DC crosstalk as a key mechanism for the regulation of gut homeostasis.
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DOI：
10.1084/jem.20111980
发表时间：
2012-02-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lindner C;Wahl B;Föhse L;Suerbaum S;Macpherson AJ;Prinz I;Pabst O
通讯作者：
Pabst O
影响因子：
64.5
作者：
Chung H;Pamp SJ;Hill JA;Surana NK;Edelman SM;Troy EB;Reading NC;Villablanca EJ;Wang S;Mora JR;Umesaki Y;Mathis D;Benoist C;Relman DA;Kasper DL
通讯作者：
Kasper DL
影响因子：
32.4
作者：
Lee YJ;Wang H;Starrett GJ;Phuong V;Jameson SC;Hogquist KA
通讯作者：
Hogquist KA
DOI：
10.1073/pnas.0802968105
发表时间：
2008-06-17
影响因子：
11.1
作者：
Barral, Patricia;Eckl-Dorna, Julia;Batista, Facundo D.
通讯作者：
Batista, Facundo D.
DOI：
10.1126/science.1188454
发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hapfelmeier S;Lawson MA;Slack E;Kirundi JK;Stoel M;Heikenwalder M;Cahenzli J;Velykoredko Y;Balmer ML;Endt K;Geuking MB;Curtiss R 3rd;McCoy KD;Macpherson AJ
通讯作者：
Macpherson AJ