Plasmacytoid Dendritic Cells Are Crucial for the Initiation of Inflammation and T Cell Immunity In Vivo

被引:177
作者
Takagi, Hideaki [1 ]
Fukaya, Tomohiro [1 ]
Eizumi, Kawori [1 ]
Sato, Yumiko [1 ]
Sato, Kaori [1 ]
Shibazaki, Azusa [1 ]
Otsuka, Haruna [1 ]
Hijikata, Atsushi [2 ]
Watanabe, Takashi [2 ]
Ohara, Osamu [2 ]
Kaisho, Tsuneyasu [3 ]
Malissen, Bernard [4 ,5 ]
Sato, Katsuaki [1 ,6 ]
机构
[1] RIKEN Res Ctr Allergy & Immunol, Lab Dendrit Cell Immunobiol, Yokohama, Kanagawa 2300045, Japan
[2] RIKEN Res Ctr Allergy & Immunol, Lab Immunogen, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan
[3] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Immune Regulat, Suita, Osaka 5650871, Japan
[4] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, Case 906, Inst Natl Sante & Rech Med U631, F-13288 Marseille 9, France
[5] Ctr Natl Rech Sci UMR6102, F-13288 Marseille 9, France
[6] PRESTO, Japan Sci & Technol Agcy, Saitama 3320012, Japan
基金
日本科学技术振兴机构;
关键词
ANTIGEN-PRESENTATION; ORAL TOLERANCE; KAPPA-B; AUTOIMMUNITY; ACTIVATION; ENGAGEMENT; INFECTION; RESPONSES; ROLES; TLR;
D O I
10.1016/j.immuni.2011.10.014
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Plasmacytoid dendritic cells (pDCs) are characterized as type I interferon-producing cells that engage endosomal toll-like receptors (TLRs) and exclusively express sialic acid binding Ig-like lectin (Siglec)-H. However, their role in vivo remains unclear. Here we report a critical role for pDCs in the regulation of inflammation and T cell immunity in vivo by using gene-targeted mice with a deficiency of Siglec-H and conditional ablation of pDCs. pDCs were required for inflammation triggered by a TLR ligand as well as by bacterial and viral infections. pDCs controlled homeostasis of effector and regulatory CD4(+) T cells. Upon antigenic stimulation and microbial infection, pDCs suppressed the induction of CD4(+) T cell responses and participated in the initiation of CD8(+) T cell responses. Furthermore, Siglec-H appeared to modulate the function of pDCs in vivo. Thus, our findings highlight previously unidentified roles of pDCs and the regulation of their function for the control of innate and adaptive immunity.
引用
收藏
页码:958 / 971
页数:14
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