Conventional and Monocyte-Derived CD11b+ Dendritic Cells Initiate and Maintain T Helper 2 Cell-Mediated Immunity to House Dust Mite Allergen
Conventional and Monocyte-Derived CD11b+ Dendritic Cells Initiate and Maintain T Helper 2 Cell-Mediated Immunity to House Dust Mite Allergen
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DOI：
10.1016/j.immuni.2012.10.016
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发表时间：
2013-02-21
期刊：
影响因子：
32.4
通讯作者：
Lambrecht, Bart N.
中科院分区：
文献类型：
--
作者：
Plantinga, Maud;Guilliams, Martin;Lambrecht, Bart N.
树突状细胞（DCs）是过敏性气道炎症发生的关键，但目前尚不清楚是哪一种DCs亚群完成这一任务。通过使用CD 64和MAR-1染色，我们可靠地分离了CD 11b（+）单核细胞来源的DC（moDC）和常规DC（cDC），并研究了肺和淋巴结（LN）DC对吸入性屋尘螨（HDM）的抗原摄取、迁移和呈递测定。主要是CD 11b（+）cDCs而不是CD 103（+）cDCs在体外HDM特异性T细胞和体内哮喘中诱导T辅助2（Th 2）细胞免疫。在缺乏所有cDC的Flt 3l（-/-）小鼠中的研究揭示，moDC也足以诱导Th 2细胞介导的免疫，但仅当给予高剂量HDM时。moDCs的主要功能是在激发过程中产生促炎趋化因子和在肺中呈递变应原。因此，我们已经确定迁移性CD 11b（+）cDCs是LN中诱导Th 2细胞介导的免疫的主要亚群，而moDCs则协调肺中的过敏性炎症。
Dendritic cells (DCs) are crucial for mounting allergic airway inflammation, but it is unclear which subset of DCs performs this task. By using CD64 and MAR-1 staining, we reliably separated CD11b(+) monocyte-derived DCs (moDCs) from conventional DCs (cDCs) and studied antigen uptake, migration, and presentation assays of lung and lymph node (LN) DCs in response to inhaled house dust mite (HDM). Mainly CD11b(+) cDCs but not CD103(+) cDCs induced T helper 2 (Th2) cell immunity in HDM-specific T cells in vitro and asthma in vivo. Studies in Flt3l(-/-) mice, lacking all cDCs, revealed that moDCs were also sufficient to induce Th2 cell-mediated immunity but only when high-dose HDM was given. The main function of moDCs was the production of proinflammatory chemokines and allergen presentation in the lung during challenge. Thus, we have identified migratory CD11b(+) cDCs as the principal subset inducing Th2 cell-mediated immunity in the LN, whereas moDCs orchestrate allergic inflammation in the lung.