Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers.
Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers.
复制标题
DOI：
10.1371/journal.pone.0250177
复制
发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Brand DD
中科院分区：
文献类型：
--
作者：
Karydis A;Sandal I;Luo J;Prislovsky A;Gamboa A;Rosloniec EF;Brand DD
我们先前的研究表明，将牙周病原体牙龈卟啉单胞菌接种到人源化B6.DR1/4小鼠的口腔中，会导致循环中Th17细胞比例增加，骨丢失，并加剧实验性自身免疫性关节炎。本研究的目的是评估包含共有表位的人类人类白细胞抗原-DRβ分子作为转基因提供给I-A˚(小鼠II类缺失)C57BL/6(B6)小鼠在驱动这些发现中所起的作用。我们比较了人源化B6.DR1(或B6.DR4)小鼠和WT(B6)小鼠的各种免疫反应参数以及牙槽骨和关节周围的骨丢失。我们发现，在接种牙龈假单胞菌的背景下，共享表位的存在增加了Th17细胞的生成百分比，显著增加了骨丢失，并且重要的是允许产生CCP2DBA/1关节炎小鼠血清中没有的⁺ACPA。由于环境因素对遗传因素的影响极其复杂，因此很难揭示导致易感个体自身免疫性关节炎的机制。这项研究的发现可能提供了这一谜题的一小部分，可以帮助我们更好地理解这种复杂性的一部分。
Our previous studies have shown that inoculation of the oral cavity of “humanized” B6.DR1/4 mice with the periodontal pathogen Porphyromonas gingivalis results in an increase in the percentage of circulating Th17 cells, loss of bone and an exacerbation of experimental autoimmune arthritis. The aim of this study was to assess the role played by the human HLA-DRβ molecule containing the shared epitope supplied as a transgene to I-A˚ (murine class II null) C57BL/6 (B6) mice in driving these findings. We compared various immune response parameters as well as alveolar and peri-articular bone loss between humanized B6.DR1 (or B6.DR4) mice and their WT (B6) counterparts. We found that the presence of the shared epitope in the context of inoculation with P. gingivalis enhanced the percentage of Th17 cells generated, dramatically enhanced bone loss and importantly allowed for the generation of CCP2⁺ ACPAs that are not found in C57BL/6 or DBA/1 arthritic mouse serum. Due to the exceedingly complex nature of environmental factors impacting on genetic elements, it has been difficult to unravel mechanisms that drive autoimmune arthritis in susceptible individuals. The findings in this study may provide one small piece of this puzzle that can help us to better understand part of this complexity.
登录
查看更多内容
影响因子：
4.3
作者：
KATZ, J;GOULTSCHIN, J;BRAUTBAR, C
通讯作者：
BRAUTBAR, C
影响因子：
4.9
作者：
Marchesan JT;Gerow EA;Schaff R;Taut AD;Shin SY;Sugai J;Brand D;Burberry A;Jorns J;Lundy SK;Nuñez G;Fox DA;Giannobile WV
通讯作者：
Giannobile WV
影响因子：
--
作者：
Wegner, Natalia;Wait, Robin;Sroka, Aneta;Eick, Sigrun;Nguyen, Ky-Anh;Lundberg, Karin;Kinloch, Andrew;Culshaw, Shauna;Potempa, Jan;Venables, Patrick J.
通讯作者：
Venables, Patrick J.
影响因子：
--
作者：
van Tilburg, MLJA;Kozarov, EV;Brady, LJ
通讯作者：
Brady, LJ
影响因子：
4.4
作者：
Wipke, BT;Wang, Z;Allen, PM
通讯作者：
Allen, PM