TLR Triggering on Tolerogenic Dendritic Cells Results in TLR2 Up-Regulation and a Reduced Proinflammatory Immune Program

被引：82

作者：

Chamorro, Sonia ^{[1
]}

Garcia-Vallejo, Juan J. ^{[1
]}

Unger, Wendy W. J. ^{[2
]}

Fernandes, Rosette J. ^{[1
]}

Bruijns, Sven C. M. ^{[1
]}

Laban, Sandra ^{[2
]}

Roep, Bart O. ^{[2
]}

't Hart, Bert A. ^{[3
]}

van Kooyk, Yvette ^{[1
]}

机构：

[1] Vrije Univ Amsterdam, Dept Mol Cell Biol & Immunol, Med Ctr, NL-1007 MB Amsterdam, Netherlands

[2] Leiden Univ, Dept Immunohematol & Blood Transfus, Med Ctr, Leiden, Netherlands

[3] Biomed Primate Res Ctr, Dept Immunobiol, Rijswijk, Netherlands

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 183卷 / 05期

关键词：

TOLL-LIKE RECEPTOR-2; NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; INDUCED LEUCINE-ZIPPER; NEGATIVE CROSS-TALK; T-CELLS; CUTTING EDGE; 1-ALPHA; 25-DIHYDROXYVITAMIN D-3; DIFFERENTIAL EXPRESSION; SIGNAL-TRANSDUCTION;

D O I：

10.4049/jimmunol.0801155

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Tolerogenic dendritic cells (TDC) offer a promising therapeutic potential to ameliorate autoimmune diseases. Reported to inhibit adaptive immune responses, little is known about their innate immunity receptor repertoire. In this study, we compared three types of human TDC (IL-10-DC, dexamethasone (DX)-DC, and 1,25(OH)(2)D-3-DC) by their TLR expression and response to a set of TLR ligands. TDC are endowed with the same TLR set as standard monocyte-derived dendritic cells but respond differentially to the TLR stimuli Pam3CSK4, polyinosinic-polycytidylic acid, LPS, and flagellin. TDC expressed low or no IL-12-related cytokines and remarkably elevated IL-10 levels. Interestingly, only TDC up-regulated the expression of TLR2 upon stimulation. This boosted the tolerogenic potential of these cells, because IL-10 production was up-regulated in TLR2-stimulated, LPS-primed DX-DC, whereas IL-12 and TNF-alpha secretion remained low. When comparing the TDC subsets, DX-DC and 1,25(OH)(2)D-3-DC up-regulated TLR2 irrespective of the TLR triggered, whereas in IL-10-DC this effect was only mediated by LPS. Likewise, DX-DC and 1,25(OH)(2)D-3-DC exhibited impaired ability to mature, reduced allostimulatory properties, and hampered capacity to induce Th1 differentiation. Therefore, both DX-DC and 1,25(OH)(2)D-3-DC display the strongest tolerogenic and anti-inflammatory features and might be most suitable tools for the treatment of autoimmune diseases. The Journal of Immunology, 2009,183: 2984-2994.

引用

页码：2984 / 2994

页数：11

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