IL-23-producing CD68+ macrophage-like cells predominate within an IL-17-polarized infiltrate in chronic periodontitis lesions
IL-23-producing CD68+ macrophage-like cells predominate within an IL-17-polarized infiltrate in chronic periodontitis lesions
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DOI：
10.1111/j.1600-051x.2011.01752.x
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发表时间：
2011-10-01
影响因子：
6.7
通讯作者：
Novak, Natalija
中科院分区：
文献类型：
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作者：
Allam, Jean-Pierre;Duan, Yonggang;Novak, Natalija
目的：目的：分析慢性牙周炎（CP）患者牙周组织中树突状细胞（DCs）、巨噬细胞（Mo）、B细胞等抗原呈递细胞（APC）的分布情况，探讨其与Th 17细胞的关系。材料与方法：采用免疫组化、免疫荧光、流式细胞术和实时荧光定量PCR等方法，对慢性牙周炎患者牙周组织中的APC进行分析。在CP病灶的底部区域观察到CD 68（+）Mo样细胞和CD 20（+）B细胞的优势以及强烈的Th 17浸润，而CD 1a（+）DCs仅在冠状区域检测到，其中Th 17浸润较低。此外，CD 68（+）Mo样细胞显示作为典型Mo标记物的CD 163表达，但平行表达典型DC标记物，如CD 11 c或CD 209和TLR 4。有趣的是，Th 17诱导细胞因子IL-23 p19由CD 68（+）Mo样细胞产生，而不是由CD 20（+）B细胞产生。牙龈卟啉单胞菌衍生的脂多糖刺激体外培养的CD 68（+）Mo样细胞后，其IL-23 p19 mRNA表达上调，TLR 4的阻断可抑制IL-23 p19 mRNA的表达。鉴于这些数据，出现了一幅图片，即CP中产生IL-17的细胞可能部分由CD 68（+）Mo样细胞指导，其在TLR 4被Pg激活后产生IL-23 p19。
Aim: To analyse antigen-presenting cells (APCs), such as dendritic cells (DCs), macrophages (Mo) or B cells depending on the regional site of chronic periodontitis (CP), and to investigate their relation to Th17 cells.Material and Methods: Biopsies from oral mucosa as well as the coronal and bottom regions of CP were analysed by immunhistochemistry, immunofluorescence, flow cytometry and real-time PCR.Results: A predominance of CD68(+) Mo-like cells and CD20(+) B cells and strong Th17 infiltration was observed in the bottom region of CP lesions, while CD1a(+) DCs were only detected in the coronal regions, where Th17 infiltration was low. Furthermore, CD68(+) Mo-like cells displayed CD163 expression as a typical Mo-marker, but expressed in parallel typical DCs markers, such as CD11c or CD209 and TLR4. Interestingly, Th17-inducing cytokine IL-23p19 was produced by CD68(+) Mo-like cells, but not CD20(+) B cells. Moreover, the stimulation of in vitro generated CD68(+) Mo-like cells by Porphyromonas gingivalis-derived (Pg) lipopolysaccharide resulted in the upregulation of their IL-23p19mRNA expression, which was inhibited by the blockage of TLR4.Conclusions: In view of these data, a picture emerges that IL-17-producing cells in CP could be in part directed by CD68(+) Mo-like cells, which produce IL-23p19 upon TLR4 activation by Pg.