Crosstalk Between Circulating Follicular T Helper Cells and Regulatory B Cells in Children With Extrinsic Atopic Dermatitis.

Crosstalk Between Circulating Follicular T Helper Cells and Regulatory B Cells in Children With Extrinsic Atopic Dermatitis.
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外源性特应性皮炎儿童循环滤泡 T 辅助细胞和调节性 B 细胞之间的串扰

DOI:
10.3389/fimmu.2021.785549
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发表时间:
2021
影响因子:
7.3
通讯作者:
Luo X
Luo X
中科院分区:
医学2区
文献类型:
--
作者:
Jiang J;Yan S;Zhou X;Zhou J;Bai X;Tan Q;Xia Y;Wang H;Luo X

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儿童早期特应性皮炎(AD)通常是高IgE相关的过敏性疾病的初始表现。越来越多的证据表明,滤泡辅助性T (Tfh)细胞在促进B细胞分化和IgE产生中起关键作用,人调节性B (Breg)细胞参与免疫调节过程和抑制过敏性炎症。然而,产生il -10的Breg细胞和Tfh细胞在儿童AD中的作用和相互作用尚不清楚。在本研究中,我们发现外源性AD患儿中CD19+IL-10+ Breg细胞的百分比显著低于年龄匹配的健康对照,并且与CD4+CXCR5+PD-1+ICOS+循环Tfh细胞反应增强和疾病活动性增加负相关;但与血清总IgE水平无显著相关性。共培养系统显示,外源性AD患者的Breg细胞不能以IL-10依赖的方式有效抑制Tfh细胞的分化。通过toll样受体(TLR)而非b细胞受体(BCR)信号通路诱导的pSTAT3信号异常可能导致AD中Breg细胞的缺陷。综上所述,这些观察结果表明产生il -10的Breg细胞在抑制Tfh细胞分化中起重要作用,并提示它们可能参与AD的发病机制。
Atopic dermatitis (AD) in early childhood is often the initial manifestation of allergic disease associated with high IgE. Accumulating evidences show that follicular helper T (Tfh) cells play a critical role in promoting B cell differentiation and IgE production, human regulatory B (Breg) cells participate in immunomodulatory processes and inhibition of allergic inflammation. However, the roles and interactions between IL-10-producing Breg cells and Tfh cells in childhood AD are unclear. In this study, we found that the percentage of CD19+IL-10+ Breg cells in children with extrinsic AD was significantly lower than that in age-matched healthy controls, and that it correlated negatively with enhanced CD4+CXCR5+PD-1+ICOS+ circulating Tfh cell responses and increased disease activity; however, there was no significant correlation with serum total IgE levels. A co-culture system revealed that Breg cells from patients with extrinsic AD cannot effectively inhibit differentiation of Tfh cells in an IL-10 dependent manner. Abnormal pSTAT3 signaling induced via Toll-like receptors (TLR), but not the B-cell receptor (BCR) signaling, might contribute to the defect of Breg cells in AD. Taken together, these observations demonstrate an important role for IL-10-producing Breg cells in inhibiting Tfh cell differentiation, and suggest that they may participate in the pathogenesis of AD.
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发表时间: 2009-06-15
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