HSP70, a Novel Regulatory Molecule in B Cell-Mediated Suppression of Autoimmune Diseases
HSP70, a Novel Regulatory Molecule in B Cell-Mediated Suppression of Autoimmune Diseases
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HSP70，一种 B 细胞介导的自身免疫性疾病抑制中的新型调节分子
DOI：
10.1016/j.jmb.2020.08.019
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发表时间：
2021-01-08
影响因子：
5.6
通讯作者：
Chu, Yiwei
中科院分区：
文献类型：
--
作者：
Wang, Luman;Fu, Ying;Chu, Yiwei
最近发现B细胞在自身免疫性疾病中起调节作用。我们之前已经证明，人外周血CD19(+)CD24(hi)CD27(+) B细胞在健康供者和自身免疫性疾病患者中都具有调节功能。然而，这种调节的机制仍未完全了解。在这项研究中，利用微阵列比较了人外周血中CD19(+)CD24(hi)CD27(+) B细胞（调节性B细胞，Bregs）与CD19(+)CD24(10)CD27(-) B细胞（非Bregs）的基因表达。我们发现热休克蛋白70 （HSP70）在Bregs中的表达显著上调。体外研究发现，抑制HSP70可损害外周血Bregs的调节功能。在自身免疫性疾病的小鼠模型中，使用HSP70缺陷小鼠或HSP70抑制剂，Bregs抑制效应细胞并挽救依赖于HSP70的疾病相关表型。在机制上，Bregs分泌HSP70，直接抑制效应细胞，如T效应细胞。这些发现表明HSP70是一种调节Breg功能的新因子，并提示增强Breg介导的HSP70的产生可能是一种治疗自身免疫性疾病的可行方法。(C) 2020作者。Elsevier Ltd.出版。
B cells have recently emerged as playing regulatory role in autoimmune diseases. We have previously demonstrated that human peripheral blood CD19(+)CD24(hi)CD27(+) 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(+)CD24(hi)CD27(+) B cells (regulatory B cells, Bregs) with CD19(+)CD24(1o)CD27(-) B cells (non-Bregs) in human peripheral blood. We found that heat shock protein 70 (HSP70) expression was significantly upregulated 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. (C) 2020 The Authors. Published by Elsevier Ltd.