Mast cell-associated TNF promotes dendritic cell migration
Mast cell-associated TNF promotes dendritic cell migration
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DOI：
10.4049/jimmunol.176.7.4102
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发表时间：
2006-04-01
影响因子：
4.4
通讯作者：
Galli, Stephen J.
中科院分区：
文献类型：
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作者：
Suto, Hajime;Nakae, Susumu;Galli, Stephen J.
肥大细胞代表TNF的潜在来源，TNF是一种可以增强树突状细胞（DC）迁移的介质。尽管肥大细胞相关的TNF在体内调节DC迁移中的重要性尚不清楚，但肥大细胞和肥大细胞衍生的TNF可以促进某些接触性超敏反应（CHS）模型的表达。我们发现，肥大细胞缺陷Kit（W-sh/W-sh）或TNF-/-小鼠中CHS对FITC的表达明显受损。Kit（W-sh/W-sh）小鼠的CHS表达减少可通过局部移植野生型骨髓源性培养肥大细胞（BMCMCs）完全修复，但TNF-/- BMCMCs只能部分修复。因此，需要肥大细胞和肥大细胞衍生的TNF来实现CHS到FITC的最佳表达。我们发现，在肥大细胞缺陷小鼠或TNF-/-小鼠中，初始小鼠表皮给予FITC 24小时后，携带FITC的皮肤DC向引流淋巴结（LNs）的迁移显著减少，但在FITC致敏后48小时，这些突变小鼠的DC迁移水平增加到大于野生型水平。肥大细胞缺陷或TNF-/-小鼠在经鼻注射FITC-OVA 24小时后，气道dc向局部LNs的迁移也显著减少。致敏24小时后，Kit（W-sh/W-sh）小鼠移植野生型而非TNF-/- BMCMCs，修复了携带fitc的dc向引流皮肤或气道的LNs的迁移。我们的研究结果表明，肥大细胞相关的TNF可以在fitc诱导的皮肤或气道dc迁移的初始阶段发挥重要作用。
Mast cells represent a potential source of TNF, a mediator which can enhance dendritic cell (DC) migration. Although the importance of mast cell-associated TNF in regulating DC migration in vivo is not clear, mast cells and mast cell-derived TNF can contribute to the expression of certain models of contact hypersensitivity (CHS). We found that CHS to FITC was significantly impaired in mast cell-deficient Kit(W-sh/W-sh) or TNF-/- mice. The reduced expression of CHS in Kit(W-sh/W-sh) mice was fully repaired by local transfer of wild-type bone marrow-derived cultured mast cells (BMCMCs), but was only partially repaired by transfer of TNF-/- BMCMCs. Thus, mast cells, and mast cell-derived TNF, were required for optimal expression of CHS to FITC. We found that the migration of FITC-bearing skin DCs into draining lymph nodes (LNs) 24 h after epicutaneous administration of FITC in naive mice was significantly reduced in mast cell-deficient or TNF-/- mice, but levels of DC migration in these mutant mice increased to greater than wild-type levels by 48 h after FITC sensitization. Mast cell-deficient or TNF-/- mice also exhibited significantly reduced migration of airway DCs to local LNs at 24 h after intranasal challenge with FITC-OVA. Migration of FITC-bearing DCs to LNs draining the skin or airways 24 h after sensitization was repaired in Kit(W-sh/W-sh) mice which had been engrafted with wild-type but not TNF-/- BMCMCs. Our findings indicate that mast cell-associated TNF can contribute significantly to the initial stages of FITC-induced migration of cutaneous or airway DCs.