LILRA2 activation inhibits dendritic cell differentiation and antigen presentation to T cells
LILRA2 activation inhibits dendritic cell differentiation and antigen presentation to T cells
复制标题
DOI：
10.4049/jimmunol.179.12.8128
复制
发表时间：
2007-12-15
影响因子：
4.4
通讯作者：
Modlin, Robert L.
中科院分区：
文献类型：
--
作者：
Lee, Delphine J.;Sieling, Peter A.;Modlin, Robert L.
单核细胞分化为树突状细胞(DC)是先天免疫系统引导适应性T细胞应答的关键机制。本研究以麻风为模型，研究了白细胞Ig样受体A2(LILRA2)对DC分化的调节作用。LILRA2蛋白在进行性麻风的皮损中表达增加，而在自限性、结核样麻风中表达增加。免疫双标记显示CD14(+)、CD68(+)单核/巨噬细胞表达LILRA2。外周血单核细胞上LILRA2的激活抑制了GM-CSF诱导的未成熟DC的分化，DC标志物(MHC II类、CD1b、CD40和CD206)的表达减少，但巨噬细胞标志物(CD209和CD14)的表达减少。此外，LILRA2的激活抑制了CD1b和MHC II类限制性麻风分枝杆菌反应性T细胞的抗原呈递，而LILRA2激活的单核细胞的细胞因子谱显示出增加了TNF-α、IL-6、IL-8、IL-12和IL-10，但对转化生长因子-β的影响很小。因此，LILRA2的激活，通过改变GM-CSF诱导的单核细胞分化为未成熟的DC，提供了一种下调天然免疫系统激活适应性T细胞反应的能力的机制，同时促进了炎症反应。
The differentiation of monocytes into dendritic cells (DC) is a key mechanism by which the innate immune system instructs the adaptive T cell response. In this study, we investigated whether leukocyte Ig-like receptor A2 (LILRA2) regulates DC differentiation by using leprosy as a model. LILRA2 protein expression was increased in the lesions of the progressive, lepromatous form vs the self-limited, tuberculoid form of leprosy. Double immunolabeling revealed LILRA2 expression on CD14(+), CD68(+) monocytes/macrophages. Activation of LILRA2 on peripheral blood monocytes impaired GM-CSF induced differentiation into immature DC, as evidenced by reduced expression of DC markers (MHC class II, CD1b, CD40, and CD206), but not macrophage markers (CD209 and CD14). Furthermore, LILRA2 activation abrogated Ag presentation to both CD1b- and MHC class II-restricted, Mycobacterium leprae-reactive T cells derived from leprosy patients, while cytokine profiles of LILRA2-activated monocytes demonstrated an increase in TNF-alpha, IL-6, IL-8, IL-12, and IL-10, but little effect on TGF-beta. Therefore, LILRA2 activation, by altering GM-CSF-induced monocyte differentiation into immature DC, provides a mechanism for down-regulating the ability of the innate immune system to activate the adaptive T cell response while promoting an inflammatory response.