Serotype b of Aggregatibacter actinomycetemcomitans increases osteoclast and memory T-lymphocyte activation.

Serotype b of Aggregatibacter actinomycetemcomitans increases osteoclast and memory T-lymphocyte activation.
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伴放线聚集杆菌 b 血清型可增加破骨细胞和记忆 T 淋巴细胞的活化。

DOI:
10.1111/omi.12112
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发表时间:
2016
影响因子:
3.7
通讯作者:
R. Vernal
R. Vernal
中科院分区:
医学3区
文献类型:
--
作者:
S. Melgar;J. Díaz;C. Alvarez;L. Rojas;G. Monasterio;P. Carvajal;A. Escobar;M. Sanz;R. Vernal

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在牙周炎期间,牙槽骨吸收与辅助性T细胞17型(Th 17)淋巴细胞和核因子-κB配体受体激活剂(RANKL)诱导的破骨细胞的活化相关。我们以前报道,血清型B的放线菌伴聚杆菌具有较高的能力,触发活化的T淋巴细胞的Th 17型分化和功能,其脂多糖是一个更有效的免疫原相比,其他血清型。本研究旨在研究伴放线菌血清型B是否诱导Th 17相关RANKL的产生、RANKL诱导的破骨细胞活化和抗原特异性记忆T淋巴细胞增殖。在用不同伴放线菌血清型致敏的自体树突状细胞刺激的初始CD 4(+)T淋巴细胞上,定量RANKL产生、T-bet、加塔-3、RORC 2和Foxp 3表达、RORC 2/RANKL细胞内双表达、TRAP(+)破骨细胞活化和骨吸收。在牙周炎和健康受试者中测定了响应伴放线菌血清型的增殖记忆T淋巴细胞的频率。与用其他血清型刺激的相同细胞相比,用血清型b致敏的树突状细胞刺激的幼稚CD 4(+)T淋巴细胞引起更高水平的RANKL、RORC 2、TRAP(+)破骨细胞和骨吸收。RANKL与RORC 2呈正相关且共表达。牙周炎患者血清B型记忆性T淋巴细胞的检出率高于健康人。这些结果表明伴放线菌血清型B与RANKL的较高产生相关,并且这些水平的增加与Th 17淋巴细胞诱导、破骨细胞活化和骨吸收相关。
During periodontitis, alveolar bone resorption is associated with activation of T helper type 17 (Th17) lymphocytes and receptor activator of nuclear factor-κB ligand (RANKL) -induced osteoclasts. We previously reported that serotype b of Aggregatibacter actinomycetemcomitans has a higher capacity to trigger Th17-type differentiation and function in activated T lymphocytes and its lipopolysaccharide is a more potent immunogen compared with the other serotypes. This study aimed to investigate whether serotype b of A. actinomycetemcomitans induces higher Th17-associated RANKL production, RANKL-induced osteoclast activation, and antigen-specific memory T lymphocyte proliferation. On naive CD4(+) T lymphocytes stimulated with autologous dendritic cells primed with different A. actinomycetemcomitans serotypes, RANKL production, T-bet, GATA-3, RORC2 and Foxp3 expression, RORC2/RANKL intracellular double-expression, TRAP(+) osteoclast activation, and bone resorption were quantified. The frequency of proliferating memory T lymphocytes in response to A. actinomycetemcomitans serotypes was determined in periodontitis and healthy subjects. Naive CD4(+) T lymphocytes stimulated by serotype b-primed dendritic cells elicited higher levels of RANKL, RORC2, TRAP(+) osteoclasts, and bone resorption than the same cells stimulated with the other serotypes. RANKL positively correlated and co-expressed with RORC2. Memory T lymphocytes responding to serotype b were more frequently detected in periodontitis patients than healthy subjects. These results indicate that serotype b of A. actinomycetemcomitans is associated with higher production of RANKL and these increased levels are associated with Th17 lymphocyte induction, osteoclast activation, and bone resorption.
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