共 55 条
Hyporesponsiveness of Intestinal Dendritic Cells to TLR Stimulation Is Limited to TLR4
被引:36
作者:

Cerovic, Vuk
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机构:
Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England

Jenkins, Christopher D.
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机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England

Barnes, Andrew G. C.
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机构:
Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England

Milling, Simon W. F.
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h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England

MacPherson, G. Gordon
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h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England

Klavinskis, Linda S.
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h-index: 0
机构:
Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England
机构:
[1] Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England
[2] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
基金:
英国生物技术与生命科学研究理事会;
关键词:
TOLL-LIKE RECEPTOR-2;
REGULATORY T-CELLS;
LAMINA-PROPRIA;
EPITHELIAL-CELLS;
CUTTING EDGE;
IN-VIVO;
FUNCTIONALLY DIFFERENT;
IMMUNE-RESPONSES;
INDUCED COLITIS;
ACTIVATION;
D O I:
10.4049/jimmunol.0802318
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Dendritic cells (DCs) are crucial to intestinal immune regulation because of their roles in inducing protective immunity against pathogens while maintaining tolerance to commensal bacteria. Nonetheless, relatively little is known about intestinal DC responsiveness to innate immune stimuli via TLRs. We have previously shown that DCs migrating from the rat intestine in lymph (iLDCs) are hyporesponsive to LPS stimulation, thus possibly preventing harmful immune responses being induced to commensal flora. In this study, to understand how iLDC function is regulated by innate immune stimuli, we have characterized the expression and function of TLRs in iLDCs isolated from the thoracic duct lymph of mesenteric lymphadenectomized rats and compared these with DCs grown from bone marrow in the presence of Flt3 ligand. We show that iLDCs express mRNAs for all TLRs, but express significantly less TLR4 mRNA than bone marrow-derived DCs. Functionally, iLDCs could be activated by TLR agonists representing intestinal pathogen-associated molecular patterns, with the important exception of the TLR4 agonist LPS. Furthermore, we show that DCs in the intestinal wall interact directly with noninvasive bacteria (Bacillus subtilis spores), leading to an increase in the output of activated iLDCs into lymph, and that DCs containing spores are activated selectively. These data highlight a functional difference between TLR4 and other TLRs. As iLDCs can respond to TLR stimulation in vitro, there must be other mechanisms that prevent their activation by commensal bacteria under steady-state conditions. The Journal of Immunology, 2009, 182: 2405-2415.
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页码:2405 / 2415
页数:11
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Japan Sci & Technol Corp, Exploratory Res Adv Technol, Suita, Osaka 5650871, Japan Osaka Univ, Host Def Lab, Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan