Mast cell migration from the skin to the draining lymph nodes upon ultraviolet irradiation represents a key step in the induction of immune suppression
Mast cell migration from the skin to the draining lymph nodes upon ultraviolet irradiation represents a key step in the induction of immune suppression
复制标题
DOI：
10.4049/jimmunol.180.7.4648
复制
发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Ullrich, Stephen E.
中科院分区：
文献类型：
--
作者：
Byrne, Scott N.;Limon-Flores, Alberto Y.;Ullrich, Stephen E.
阳光中的紫外线辐射是皮肤癌的主要原因。紫外线还具有免疫抑制作用，大量研究表明，紫外线诱导的免疫抑制是诱发皮肤癌的主要危险因素。以往的研究表明，真皮肥大细胞在诱导免疫抑制中起关键作用。肥大细胞缺陷小鼠对紫外线辐射的免疫抑制作用具有抗性，通过将骨髓来源的肥大细胞注射到肥大细胞缺陷小鼠的皮肤中可以恢复紫外线诱导的免疫抑制。然而，肥大细胞促进免疫抑制的确切过程尚不清楚。在这项研究中，我们表明在诱导免疫抑制的第一步是肥大细胞从皮肤迁移到引流淋巴结。紫外线照射，以剂量依赖的方式，导致淋巴结肥大细胞数量显著增加。当将GFP（+）皮肤移植到肥大细胞缺陷小鼠身上时，我们发现GFP（+）肥大细胞优先迁移到引流皮肤的淋巴结中。肥大细胞主要迁移到引流淋巴结的B细胞区。肥大细胞表达CXCR4(+)，紫外线照射可上调其配体CXCL12在淋巴结B细胞中的表达。用CXCR4拮抗剂处理紫外线照射小鼠可阻断肥大细胞迁移并消除紫外线诱导的免疫抑制。我们的研究结果表明，由CXCR4与CXCL12相互作用介导的紫外线诱导的肥大细胞向引流淋巴结的迁移是紫外线诱导免疫抑制的关键早期步骤。
The UV radiation in sunlight is the primary cause of skin cancer. UV is also immunosuppressive and numerous studies have shown that UV-induced immune suppression is a major risk factor for skin cancer induction. Previous studies demonstrated that dermal mast cells play a critical role in the induction of immune suppression. Mast cell-deficient mice are resistant to the immunosuppressive effects of UV radiation, and UV-induced immune suppression can be restored by injecting bone marrow-derived mast cells into the skin of mast cell-deficient mice. The exact process however, by which mast cells contribute to immune suppression, is not known. In this study, we show that one of the first steps in the induction of immune suppression is mast cell migration from the skin to the draining lymph nodes. UV exposure, in a dose-dependent manner, causes a significant increase in lymph node mast cell numbers. When GFP(+) skin was grafted onto mast cell-deficient mice, we found that GFP(+) mast cells preferentially migrated into the lymph nodes draining the skin. The mast cells migrated primarily to the B cell areas of the draining nodes. Mast cells express CXCR4(+) and UV exposure up-regulated the expression of its ligand CXCL12 by lymph node B cells. Treating UV-irradiated mice with a CXCR4 antagonist blocked mast cell migration and abrogated UV-induced immune suppression. Our findings indicate that UV-induced mast cell migration to draining lymph nodes, mediated by CXCR4 interacting with CXCL12, represents a key early step in UV-induced immune suppression.