Leucocyte-associated immunoglobulin-like receptor-1 is an inhibitory regulator of contact hypersensitivity
Leucocyte-associated immunoglobulin-like receptor-1 is an inhibitory regulator of contact hypersensitivity
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DOI：
10.1111/j.1365-2567.2009.03140.x
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发表时间：
2009-12-01
期刊：
影响因子：
6.4
通讯作者：
Tamada, Koji
中科院分区：
文献类型：
--
作者：
Omiya, Ryusuke;Tsushima, Fumihiko;Tamada, Koji
白细胞相关免疫球蛋白样受体-1（LAIR-1）是免疫球蛋白（IG）超家族的一种膜受体，表达于大多数造血细胞上，通过与胶原蛋白相互作用传递抑制信号。为了阐明LAIR-1在体内的免疫学功能，我们建立了表达由LAIR-1的胞外结构域与IG标签融合组成的嵌合蛋白（LAIR-1-IG）的转基因小鼠，其通过与内源性LAIR-1竞争而充当诱饵。转基因小鼠表现出对接触性超敏反应（CHS）的易感性增加，这是一种过敏性接触性皮炎的实验模型，与增强的半抗原特异性T细胞应答相关。当将来自半抗原致敏供体小鼠的T细胞转移到非致敏受体中时，用LAIR-1-IG蛋白处理供体小鼠或受体小鼠加速CHS，表明LAIR-1在致敏和诱导半抗原反应性T细胞中的潜在负面作用。体外实验表明，LAIR-1可抑制树突状细胞产生白细胞介素-6和白细胞介素-12，抑制幼稚T细胞和记忆T细胞的增殖和细胞因子的产生，并伴有沿着G（0）/G（1）细胞周期阻滞。总的来说，我们的研究结果表明，LAIR-1通过调节抗原呈递细胞和T细胞功能在CHS中起着至关重要的抑制作用。
P>Leucocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a membrane receptor of the immunoglobulin (Ig) superfamily that is expressed on most types of haematopoietic cells, and delivers inhibitory signals through interacting with collagens. In order to elucidate the immunological functions of LAIR-1 in vivo, we established transgenic mice expressing a chimeric protein composed of the extracellular domain of LAIR-1 fused with an Ig tag (LAIR-1-Ig), which acts as a decoy by competing with endogenous LAIR-1. The transgenic mice showed an increased susceptibility for development of contact hypersensitivity (CHS), an experimental model of allergic contact dermatitis, in association with enhanced hapten-specific T-cell responses. When T cells from the hapten-sensitized donor mice were transferred into non-sensitized recipients, treatment of either donor mice or recipient mice with LAIR-1-Ig protein accelerated CHS, suggesting a potentially negative role of LAIR-1 in both the sensitization and the elicitation of hapten-reactive T cells. In vitro assays revealed that LAIR-1 decreased the production of interleukin-6 and interleukin-12 in dendritic cells, and inhibited the proliferation and cytokine production of naive and memory T cells along with G(0)/G(1) cell cycle arrest. Collectively, our findings suggest that LAIR-1 plays a crucial inhibitory role in CHS by regulating antigen-presenting cell and T-cell functions.