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HSP70, a Novel Regulatory Molecule in B Cell-Mediated Suppression of Autoimmune Diseases.
Journal of Molecular Biology ( IF 4.7 ) Pub Date : 2020-08-26 , DOI: 10.1016/j.jmb.2020.08.019
Luman Wang 1 , Ying Fu 2 , Baichao Yu 2 , Xuechao Jiang 2 , Hongchun Liu 3 , Jun Liu 4 , Bingbing Zha 4 , Yiwei Chu 5
Affiliation  

B cells have recently emerged as playing regulatory role in autoimmune diseases. We have previously demonstrated that human peripheral blood CD19+ CD24hiCD27+ B cells have regulatory function both in healthy donors and in patients with autoimmune disease. However, the mechanism of this regulation is still not fully understood. In this study, microarrays were utilized to compare gene expression of CD19+ CD24hiCD27+ B cells (regulatory B cells, Bregs) with CD19+ CD24loCD27 B cells (non-Bregs) in human peripheral blood. We found that heat shock protein 70 (HSP70) expression was significantly up regulated in Bregs. In vitro studies explored that HSP70 inhibition impaired the regulatory function of peripheral blood Bregs. In mouse models of autoimmune disease, using HSP70-deficient mice or HSP70 inhibitors, Bregs suppressed effector cells and rescued disease-associated phenotypes that were dependent on HSP70. Mechanistically, Bregs secreted HSP70, directly suppressing effector cells, such as T effect cells. These findings reveal that HSP70 is a novel factor that modulates Breg function and suggest that enhancing Breg-mediated production of HSP70 could be a viable therapy for autoimmune disease.



中文翻译:

HSP70,B细胞介导的自身免疫性疾病抑制中的新型调节分子。

B细胞最近在自身免疫性疾病中起着调节作用。先前我们已经证明,人外周血CD19 +  CD24 hi CD27 + B细胞在健康供体和自身免疫性疾病患者中均具有调节功能。但是,该法规的机制仍不完全清楚。在这项研究中,微阵列用于CD19的基因表达比较+  CD24CD27 + B细胞(调节性B细胞,Bregs)与CD19 +  CD24 LO CD27 -人外周血中的B细胞(非Bregs)。我们发现热休克蛋白70(HSP70)表达在Bregs中明显上调。体外研究探索了HSP70抑制作用会削弱外周血Breg的调节功能。在自身免疫性疾病的小鼠模型中,使用HSP70缺陷型小鼠或HSP70抑制剂,Bregs抑制了效应细胞并拯救了依赖于HSP70的疾病相关表型。在机制上,布雷格斯分泌HSP70,直接抑制效应细胞,如T效应细胞。这些发现表明,HSP70是调节Breg功能的新型因子,并表明增强Breg介导的HSP70的产生可能是治疗自身免疫性疾病的可行方法。

更新日期:2020-08-26
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