首页> 外文期刊>Cell stress & chaperones >Autologous extracellular Hsp70 exerts a dual role in rheumatoid arthritis
【24h】

Autologous extracellular Hsp70 exerts a dual role in rheumatoid arthritis

机译:自体细胞外HSP70在类风湿性关节炎中发挥双重作用

获取原文
       

摘要

Extracellular heat shock proteins (Hsp) influence the adaptive immune response and may ameliorate pathogenesis of autoimmune diseases. While some preclinical observations suggest that highly conserved bacterial and/or murine Hsp70 peptides have potential utility in treatment of rheumatoid arthritis (RA) via induction of T regulatory cells (Treg), the role of extracellular inducible human Hsp70 in adaptive immune processes requires further investigation. The present study evaluated Hsp70 influence on inflammatory cytokine-mediated modulation of T cell immunophenotype in ways that influence RA onset and severity. Initial experiments in the present investigation revealed that serum levels of Hsp70 are approximately 2-fold higher in RA patients versus healthy control subjects. To explore the effect of extracellular Hsp70 on key processes underlying the adaptive immune system, the effects of a highly pure, substrate-, and endotoxin-free human Hsp70 on polarization of the T helper cell subpopulations, including CD4 ~(+)IL-17 ~(+) (Th17), CD4 ~(+)FoxP3 ~(+) (Treg), CD4 ~(+)IFN-γ ~(+) (Th1), and CD4 ~(+)IL-4 ~(+) (Th2), were studied in na?ve human peripheral blood mononuclear cell (PBMC) cultures stimulated with anti-CD3/28 mAb. Major findings included an observation that while Hsp70 treatment increased Th17 frequencies and Th17/Treg ratio, the frequency of Th1 cells and the Th1/Th2 ratio were significantly decreased in the Hsp70-treated PBMC cultures. Moreover, data shown here provides preliminary suggestion that major contributing Hsp70-mediated immunomodulation includes interleukin 6 (IL-6) influence on Th17/Treg and Th1/Th2, since expression of this inflammatory cytokine is enhanced by in vitro Hsp70 treatment. These results are nevertheless preliminary and require further investigation to validate the above model.
机译:细胞外热休克蛋白(HSP)影响适应性免疫应答,可改善自身免疫疾病的发病机制。虽然一些临床前观察结果表明,高度保守的细菌和/或鼠HSP70肽通过诱导T调节细胞(Treg)治疗类风湿性关节炎(RA),但细胞外诱导人HSP70在适应性免疫过程中的作用需要进一步调查。本研究评估了HSP70对炎性细胞因子介导的T细胞免疫蛋白型调节的影响,以影响RA发作和严重程度。本研究中的初步实验表明,RA患者的HSP70血清Hsp70大约高2倍,与健康对照受试者相比较高。为了探讨细胞外HSP70对自适应免疫系统的关键过程的影响,高纯度,基质和内毒素和内毒素的人HSP70对T辅助细胞群偏振的影响,包括CD4〜(+)IL-17 〜(+)(TH17),CD4〜(+)FOXP3〜(+)(Treg),CD4〜(+)IFN-γ〜(+)(TH1),以及CD4〜(+)IL-4〜(+ )(th2),在Na've人外周血单核细胞(PBMC)培养物中用抗CD3 / 28mAb刺激。主要发现包括观察结果,而HSP70治疗增加的频率和Th17 / Treg比率,HSP70处理的PBMC培养物中Th1细胞的频率和Th1 / Th2的比率显着降低。此外,这里所示的数据提供了初步建议,即HSP70介导的免疫调节主要有助于HeShein 6(IL-6)对Th17 / Treg和Th1 / Th2的影响,因为通过体外HSP70治疗增强了这种炎性细胞因子的表达。然而,这些结果仍然是初步的,需要进一步调查来验证上述模型。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号