Lung dendritic cells have a potent capability to induce production of immunoglobulin A
Lung dendritic cells have a potent capability to induce production of immunoglobulin A
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DOI：
10.1165/rcmb.2007-0237oc
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发表时间：
2008-02-01
影响因子：
6.4
通讯作者：
Nakamura, Hirotoshi
中科院分区：
文献类型：
--
作者：
Naito, Tateaki;Suda, Takafumi;Nakamura, Hirotoshi
粘膜免疫系统提供了抵抗肺部吸入病原体的第一道防线。该系统主要由浆细胞局部产生的免疫球蛋白A（IgA）介导，所述浆细胞来源于归巢IgA定向B细胞。尚未确定哪种类型的抗原呈递细胞（APC）主要诱导肺中B细胞分化以产生伊加。此外，虽然粘膜树突状细胞（DC）在功能上不同于其他组织中的DC，但尚不清楚粘膜肺DC（LDC）和非粘膜DC之间的IgA表达能力是否不同。本研究旨在鉴定主要负责肺内伊加诱导的APC，并确定最不发达国家和非粘膜DC之间IgA-inclucing能力的潜在差异。我们测量了免疫球蛋白和细胞因子的产生在共培养系统中含有幼稚IgD（+）B细胞，幼稚T细胞从卵清蛋白特异性T细胞受体转基因小鼠，和APC，包括最不发达国家，肺泡巨噬细胞（AM），或脾树突状细胞（SDC）。最不发达国家诱导显着更高水平的伊加，IgG 1，IL-6，TGF-β比AM和SDCs，而没有发现在生产IgM或IgG 2a的差异。此外，总类别转换免疫球蛋白的伊加百分比最高的共培养物与最不发达国家（38.4%）相比，与AM（15.1%）和SDC（22.7%）。中和TGF-β，而不是IL-6，显着降低伊加诱导的最不发达国家和SDCs，但不是由AM。本研究表明，最不发达国家是主要的APC介绍伊加到肺，并有更强大的IgA-inclucing能力比nonmucosal DCs。
The mucosal immune system provides the first line of defense against inhaled pathogens in the lung. This system is largely mediated by immunoglobulin A (lgA) locally produced by plasma cells, which originate from homing IgA-committed B cells. It has not been determined what types of antigen-presenting cells (APCs) primarily induce B cell differentiation for IgA production in the lung. In addition, although mucosal dendritic cells (DCs) are functionally distinct from DCs in other tissues, it is unclear whether IgA-inclucing capability differs between mucosal lung DCs (LDCs) and nonmucosal DCs. The present study was conducted to identify APCs principally responsible for IgA induction in the lung, and to determine potential differences in IgA-inclucing capacity between LDCs and nonmucosal DCs. We measured immunoglobulin and cytokine production in a coculture system containing naive IgD(+) B cells, naive T cells from ovalbumin-specific T cell-receptor transgenic mice, and APCs including LDCs, alveolar macrophages (AMs), or spleen DCs (SDCs). LDCs induced significantly greater levels of IgA, IgG1, IL-6, and TGF-beta than AMs and SDCs, whereas no differences were found in the production of IgM or IgG2a. In addition, the IgA percentage of total class-switched immunoglobulin was highest in cocultures with LDCs (38.4%) when compared with those with AMs (15.1%) and SDCs (22.7%). Neutralizing TGF-beta, but not IL-6, significantly decreased IgA induction by LDCs and SDCs, but not by AMs. This study suggests that LDCs are the primary APCs introducing IgA to the lung, and have a more potent IgA-inclucing capacity than nonmucosal DCs.