Dysfunction of CD19(+)CD24(hi)CD27(+) B regulatory cells in patients with bullous pemphigoid.
Dysfunction of CD19(+)CD24(hi)CD27(+) B regulatory cells in patients with bullous pemphigoid.
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DOI：
10.1038/s41598-018-19226-z
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发表时间：
2018-01-15
影响因子：
4.6
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Liu Z;Dang E;Li B;Qiao H;Jin L;Zhang J;Wang G
大疱性类天疱疮（BP）是一种自身免疫性起泡性皮肤病，其特征是产生针对半桥粒蛋白BP 180的自身抗体。B调节细胞（BCRs）在维持自身耐受性和抑制自身抗体产生中至关重要。然而，目前尚不清楚是否BELF的功能障碍有助于BP患者自身抗体的产生。本研究发现，BP患者外周血中CD 19 + CD 24、hiCD 27 + Bcl 2和IL-10+ CD 19 + Bcl 2表达水平较健康对照组明显升高。此外，与来自健康个体的BMPs相比，我们发现来自BP患者的BMPs在与患者来源的PBMC共培养时不能抑制特异性抗BP 180自身抗体的产生。此外，BP患者的Bcl 4对CD 4 + T细胞增殖和细胞因子（包括IFN-γ、TNF-α和IL-4）表达的抑制作用不明显。值得注意的是，我们发现患者源性BAE产生高水平的TNF-α，并且TNF抑制剂依那西普可以抑制体外培养系统中自身抗体的产生。我们的研究结果表明，从BP患者的BRESINS出现表型促炎的细胞因子谱和免疫抑制功能的缺陷，这表明，BRESINS发挥促炎作用，而不是在BP的发病机制中的调节作用。
Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by the production of autoantibodies against the hemidesmosomal protein BP180. B regulatory cells (Bregs) are crucial in maintaining self-tolerance and suppressing autoantibody production. However, it is still unclear whether the dysfunctions of Bregs contributes to the autoantibody production in BP patients. In this study, we found that CD19+CD24hiCD27+ Bregs and IL-10+CD19+ Bregs were significantly increased in the peripheral blood samples of BP patients compared with that in healthy controls. Moreover, compared to Bregs from healthy individuals, we found that Bregs from BP patients fails to suppress the production of specific anti-BP180 autoantibody when co-cultured with patient-derived PBMCs. Additionally, Bregs from BP patients were defective in suppressing the CD4+ T cell proliferation and the cytokines expression (including IFN-γ, TNF-α and IL-4). Notably, we found that patient-derived Bregs produced high level of TNF-α and the TNF inhibitor etanercept could inhibit the autoantibody production in the culture system in vitro. Our results indicate that Bregs from BP patient appear phenotypically pro-inflammatory by their cytokine profile and are defective in immunosuppressive function, which suggest that Bregs play a pro-inflammatory role rather than a regulatory role in the pathogenesis of BP.
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影响因子：
4.4
作者：
Heo, Yu-Jung;Joo, Young-Bin;Min, Jun-Ki
通讯作者：
Min, Jun-Ki
影响因子：
4.4
作者：
Hedrich CM;Bream JH
通讯作者：
Bream JH
DOI：
10.1084/jem.20021293
发表时间：
2003-02-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mauri C;Gray D;Mushtaq N;Londei M
通讯作者：
Londei M
影响因子：
17.1
作者：
Flores-Borja, Fabian;Bosma, Anneleen;Mauri, Claudia
通讯作者：
Mauri, Claudia
DOI：
10.4049/jimmunol.1500559
发表时间：
2015-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ali MF;Driscoll CB;Walters PR;Limper AH;Carmona EM
通讯作者：
Carmona EM