MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties.
MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties.
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DOI：
10.4049/jimmunol.1003740
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发表时间：
2011-07-01
期刊：
影响因子：
--
通讯作者：
Mora JR
中科院分区：
文献类型：
--
作者：
Wang S;Villablanca EJ;De Calisto J;Gomes DC;Nguyen DD;Mizoguchi E;Kagan JC;Reinecker HC;Hacohen N;Nagler C;Xavier RJ;Rossi-Bergmann B;Chen YB;Blomhoff R;Snapper SB;Mora JR
肠道相关树突状细胞（DC）合成全反式视黄酸（RA），这是诱导肠道嗜性淋巴细胞所必需的。来自 MyD88-/- 小鼠的肠道相关 DC 缺乏大多数 TLR 信号，表达低水平的视网膜脱氢酶（Raldh，RA 生物合成的关键酶），并且诱导肠道归巢 T 细胞的能力显着受损。用 TLR1/2 激动剂预处理肠外 DC 足以诱导 Raldh 并赋予这些 DC 通过依赖 MyD88 和 JNK/MAPK 的机制诱导肠道归巢淋巴细胞的能力。此外，来自TLR2-/-小鼠或JNK被药理学阻断的小鼠的肠道相关DC在印记肠道归巢T细胞的训练中受到损害，这与免疫后TLR2-/-小鼠中肠道亲性T细胞的诱导减少相关。因此，MyD88依赖性TLR2信号对于培养DC具有肠道特异性印记特性是必要且充分的，并有助于在体内产生肠道亲性T细胞。
Gut-associated dendritic cells (DC) synthesize all-trans retinoic acid (RA), which is required for inducing gut-tropic lymphocytes. Gut-associated DC from MyD88-/- mice, which lack most TLR signals, expressed low levels of retinal dehydrogenases (Raldh, critical enzymes for RA biosynthesis) and were significantly impaired in their capacity to induce gut-homing T cells. Pre-treatment of extra-intestinal DC with a TLR1/2 agonist was sufficient to induce Raldh and to confer these DC with the capacity to induce gut-homing lymphocytes via a mechanism dependent on MyD88 and JNK/MAPK. Moreover, gut-associated DC from TLR2-/- mice or from mice in which JNK was pharmacologically blocked were impaired in their education to imprint gut-homing T cells, which correlated with a decreased induction of gut-tropic T cells in TLR2-/- mice upon immunization. Thus, MyD88-dependent TLR2 signals are necessary and sufficient to educate DC with gut-specific imprinting properties and contribute in vivo to the generation of gut-tropic T cells.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
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影响因子：
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