Mast cells are crucial for early inflammation, migration of Langerhans cells, and CTL responses following topical application of TLR7 ligand in mice
Mast cells are crucial for early inflammation, migration of Langerhans cells, and CTL responses following topical application of TLR7 ligand in mice
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DOI：
10.1182/blood-2006-07-036889
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发表时间：
2007-08-01
期刊：
影响因子：
20.3
通讯作者：
Stassen, Michael
中科院分区：
文献类型：
--
作者：
Heib, Valeska;Becker, Marc;Stassen, Michael
直到最近，ige激活的肥大细胞被认为仅仅是适应性免疫反应的效应细胞，参与过敏反应和对寄生虫的粘膜免疫。在此，我们报告了小鼠真皮肥大细胞，通过局部给药含有合成TLR7配体咪喹莫特的乳膏激活，是启动早期炎症反应所必需的。肥大细胞来源的细胞因子tnf - α和IL-1 β在这一过程中起重要作用。此外，tlr7激活的肥大细胞也能够促进朗格汉斯细胞的迁移，这部分取决于肥大细胞来源的IL-1 β的表达。我们之前的研究表明，TLR7结扎增强了局部应用于皮肤的疫苗抗原引起的经皮免疫，这是一种直接针对皮肤上驻留的抗原呈递细胞的程序。因此，我们现在在这里证明，使用咪喹莫特作为佐剂经皮免疫后，在肥大细胞缺陷小鼠中产生肽特异性细胞毒性t淋巴细胞反应的能力严重受损。因此，这些发现证明了替代激活肥大细胞在先天免疫和适应性免疫界面上的强大通用性。
Until recently, IgE-activated mast cells have been regarded merely as effector cells of adaptive immune responses, involved in allergic reactions and mucosal immunity to parasites. Herein, we report that murine dermal mast cells, activated by local administration of a cream containing the synthetic TLR7 ligand imiquimod, are essential to initiate an early inflammatory reaction. The mast-cell-derived cytokines TNF-alpha and IL-1 beta play an important role in this process. Furthermore, TLR7-activated mast cells are also able to promote the emigration of Langerhans cells, which partly depends on the expression of mast-cell-derived IL-1 beta. We have previously shown that TLR7 ligation enhances transcutaneous immunization evoked by topical application of vaccine antigens to the skin, a procedure that directly targets skin-resident antigen-presenting cells. Consequently, we now demonstrate here that the capacity to mount a peptide-specific cytotoxic T-lymphocyte response following transcutaneous immunization using imiquimod as adjuvant is severely impaired in mast-cell-deficient mice. Thus, these findings demonstrate the potent versability of alternatively activated mast cells at the interface of innate and adaptive immunity.