NOD2 ligation subverts IFN-alpha production by liver plasmacytoid dendritic cells and inhibits their T cell allostimulatory activity via B7-H1 up-regulation.
NOD2 ligation subverts IFN-alpha production by liver plasmacytoid dendritic cells and inhibits their T cell allostimulatory activity via B7-H1 up-regulation.
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DOI：
10.4049/jimmunol.0900582
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发表时间：
2009-12-01
期刊：
影响因子：
--
通讯作者：
Thomson AW
中科院分区：
文献类型：
--
作者：
Castellaneta A;Sumpter TL;Chen L;Tokita D;Thomson AW
核苷酸结合寡聚结构域（NOD）2/CARD15蛋白感知细菌肽聚糖产物muramyl二肽（MDP），在调节肠道免疫中起重要作用。虽然肝脏暴露于肠源性MDP，但NOD2结扎对肝APC，特别是树突状细胞（DC）的影响尚不清楚。新分离的小鼠肝脏和脾脏浆细胞样(p)DC表达的NOD2信息水平高于常规髓细胞样(m)DC。在体内MDP刺激后，肝脏pDC（而非mDC）上调IFN调节因子4 （IFN regulatory factor 4，一种TLR信号的负调节因子）的表达，诱导异体T细胞增殖和IFNγ产生减少。在体内，它们的过继转移未能引起同种异体T细胞。相比之下，脾DC IRF4水平和T细胞刺激活性保持不变。与对照组相比，mdp刺激小鼠的肝pDC显示出更高的i - b α、细胞表面B7-H1和B7-H1。在肝脏mDC或脾脏DC中未观察到类似的效果。缺乏B7-H1对肝pDC的抑制作用逆转了MDP的抑制作用。在体外LPS或CpG刺激后，与对照组相比，经mdp处理的动物肝脏pDC分泌的IL-12p70、IL-6和tnf - α减少，诱导的同种异体T细胞增殖较弱。此外，CpG刺激的dp处理小鼠的肝脏pDC分泌的IFNα少于对照组的脾脏pDC，并且在给予CpG后，dp处理小鼠的全身IFNα水平降低。这些发现表明，NOD2结扎对肝pDC的不同影响可能在调节肝脏先天免疫和适应性免疫中发挥作用。
Nucleotide-binding oligomerization domain (NOD)2/CARD15 protein, that senses muramyl dipeptide (MDP), a product of bacterial peptidoglycan, appears to play an important role in regulating intestinal immunity. Although the liver is exposed to gut-derived MDP, the influence of NOD2 ligation on hepatic APC, in particular dendritic cells (DC), is unknown. Freshly-isolated mouse liver and spleen plasmacytoid (p)DC expressed higher levels of NOD2 message than conventional myeloid (m)DC. Following MDP stimulation in vivo, liver pDC, but not mDC, upregulated expression of IFN regulatory factor 4 (IRF4), a negative regulator of TLR signaling, and induced less allogeneic T cell proliferation and IFNγ production. Their adoptive transfer failed to prime allogeneic T cells in vivo. By contrast, splenic DC IRF4 levels and T cell stimulatory activity remained unchanged. Liver pDC from MDP-stimulated mice also displayed greater IκBα, cell surface B7-H1, and B7-H1 relative to CD86 than control liver pDC. No similar effects were observed for liver mDC or spleen DC. Absence of B7-H1 on liver pDC reversed the inhibitory effect of MDP. After ex vivo stimulation with LPS or CpG, liver pDC but not mDC from MDP-treated animals secreted less IL-12p70, IL-6 and TNFα and induced weaker allogeneic T cell proliferation than those from controls. Moreover, CpG-stimulated liver pDC from MDP-treated mice secreted less IFNα than their splenic counterparts, and systemic levels of IFNα were reduced in MDP-treated animals after CpG administration. These findings suggest that differential effects of NOD2 ligation on liver pDC may play a role in regulating hepatic innate and adaptive immunity.
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影响因子：
32.4
作者：
Dong, HD;Zhu, GF;Chen, LP
通讯作者：
Chen, LP
影响因子：
32.4
作者：
Goubier, Anne;Dubois, Bertrand;Gheit, Hanane;Joubert, Grgoire;Villard-Truc, Florence;Asselin-Paturel, Carine;Trinchieri, Giorgio;Kaiserlian, Dominique
通讯作者：
Kaiserlian, Dominique
影响因子：
4.8
作者：
Gutierrez, O;Pipaon, C;Fernandez-Luna, JL
通讯作者：
Fernandez-Luna, JL
影响因子：
168.9
作者：
Hampe, J;Grebe, J;Schreiber, S
通讯作者：
Schreiber, S
DOI：
10.4049/jimmunol.0803404
发表时间：
2009-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bamboat ZM;Stableford JA;Plitas G;Burt BM;Nguyen HM;Welles AP;Gonen M;Young JW;DeMatteo RP
通讯作者：
DeMatteo RP