Dendritic cells are crucial for maintenance of tertiary lymphoid structures in the lung of influenza virus-infected mice.
Dendritic cells are crucial for maintenance of tertiary lymphoid structures in the lung of influenza virus-infected mice.
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树突状细胞对于维持流感病毒感染小鼠肺部的三级淋巴结构至关重要。
DOI：
10.1084/jem.20090410
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发表时间：
2009-10-26
期刊：
影响因子：
--
通讯作者：
Lambrecht BN
中科院分区：
文献类型：
--
作者：
GeurtsvanKessel CH;Willart MA;Bergen IM;van Rijt LS;Muskens F;Elewaut D;Osterhaus AD;Hendriks R;Rimmelzwaan GF;Lambrecht BN
三级淋巴器官（TLOs）是B细胞和T细胞的有组织聚集体，在胚胎后生命期因对感染因子或自身抗原的慢性免疫应答而形成。尽管CD11c⁺树突状细胞（DCs）一直存在于TLO区域，但其对TLO组织的贡献尚未得到详细研究。我们发现CD11c⁺⁺ DCs对诱导性支气管相关淋巴组织（iBALT）的维持至关重要，iBALT是流感病毒感染后在肺部诱导产生的一种TLO。在病毒从肺部清除后去除DCs会导致iBALT解体以及生发中心（GC）反应减少，这使得肺部和骨髓中类别转换的浆细胞数量显著减少，并且保护性抗病毒血清免疫球蛋白也减少。从机制上讲，从患有iBALT的小鼠肺部分离出的DCs不再向T细胞呈递病毒抗原，而是成为淋巴毒素（LT）β和稳态趋化因子（CXCL - 12、 - 13以及CCL - 19、 - 21）的来源，已知这些因子有助于TLO的组织。与去除DCs一样，在病毒清除后阻断LTβ受体信号会导致iBALT解体和GC反应消失。总之，我们的数据揭示了肺部DCs在iBALT内稳态和对流感病毒的体液免疫中一种先前未被重视的功能。
Tertiary lymphoid organs (TLOs) are organized aggregates of B and T cells formed in postembryonic life in response to chronic immune responses to infectious agents or self-antigens. Although CD11c+ dendritic cells (DCs) are consistently found in regions of TLO, their contribution to TLO organization has not been studied in detail. We found that CD11chi DCs are essential for the maintenance of inducible bronchus-associated lymphoid tissue (iBALT), a form of TLO induced in the lungs after influenza virus infection. Elimination of DCs after the virus had been cleared from the lung resulted in iBALT disintegration and reduction in germinal center (GC) reactions, which led to significantly reduced numbers of class-switched plasma cells in the lung and bone marrow and reduction in protective antiviral serum immunoglobulins. Mechanistically, DCs isolated from the lungs of mice with iBALT no longer presented viral antigens to T cells but were a source of lymphotoxin (LT) β and homeostatic chemokines (CXCL-12 and -13 and CCL-19 and -21) known to contribute to TLO organization. Like depletion of DCs, blockade of LTβ receptor signaling after virus clearance led to disintegration of iBALT and GC reactions. Together, our data reveal a previously unappreciated function of lung DCs in iBALT homeostasis and humoral immunity to influenza virus.
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