Aberrant Expansion and Function of Follicular Helper T Cell Subsets in IgG4-Related Disease
Aberrant Expansion and Function of Follicular Helper T Cell Subsets in IgG4-Related Disease
复制标题
IgG4 相关疾病中滤泡辅助 T 细胞亚群的异常扩张和功能
DOI：
10.1002/art.40556
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发表时间：
2018-11-01
影响因子：
13.3
通讯作者：
Lipsky, Peter E.
中科院分区：
文献类型：
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作者：
Chen, Yu;Lin, Wei;Lipsky, Peter E.
方法检测IgG 4相关性疾病（IgG 4-RD）患者外周血单个核细胞中Tfh细胞及其亚群的数量和功能，以及B细胞淋巴瘤6（Bcl-6）、B淋巴细胞诱导成熟蛋白1（BLIMP-1）、和白细胞介素-21（IL-21）信使RNA（mRNA）。采用免疫组织化学和免疫荧光技术检测患者的受累组织中IL-21、Bcl-6和CD 4 + CXCR 5 + Tfh细胞的定位。此外，循环转铁蛋白（CTfh）细胞亚群诱导B细胞增殖，凋亡和分化，并产生IgG 4的能力进行了探讨，在体外cocultures. ResultsConclusioncTfh细胞的频率显着增加，在外周血中的IgG 4-RD患者，甚至更高的频率观察到在所涉及的组织。CD 4 + CXCR 5 +ICOS+ cTfh细胞中程序性细胞死亡蛋白1的表达与血清IgG和IgG 4水平、IgG 4：IgG比值、受累器官数、CD 19 + CD 24-CD 38（高）浆母细胞/浆细胞频率呈正相关。与健康对照组相比，IgG 4-RD患者外周血CD 4 + T细胞中的BLIMP-1和IL-21 mRNA水平升高，并且这与血清IgG 4水平相关。此外，在受累组织中，Bcl-6、IL-21和Tfh细胞高度表达。与健康对照cTfh细胞相比，IgG 4-RD患者cTfh细胞能更有效地促进B细胞增殖和抑制B细胞凋亡，并促进幼稚B细胞向转换记忆B细胞和浆母细胞/浆细胞分化，从而增加IgG 4的分泌。值得注意的是，cTfh 1和cTfh 2细胞亚群在提供B细胞帮助方面是最有效的。Tfh细胞亚群在IgG 4-RD中扩增，并且可能在疾病的发病机制中起关键作用。
ObjectiveMethodsTo determine the number and function of follicular helper T (Tfh) cell subsets in IgG4-related disease (IgG4-RD).Mononuclear cells from the peripheral blood and involved tissue of patients with IgG4-RD were assessed for Tfh cells and their subsets, and levels of B cell lymphoma 6 (Bcl-6), B lymphocyte-induced maturation protein 1 (BLIMP-1), and interleukin-21 (IL-21) messenger RNA (mRNA). Immunohistochemical and immunofluorescence techniques were used to assess the involved tissue of patients to determine the location of IL-21, Bcl-6, and CD4+CXCR5+ Tfh cells. Furthermore, the ability of circulating Tfh (cTfh) cell subsets to induce B cell proliferation, apoptosis, and differentiation and to produce IgG4 was explored in cell cocultures in vitro.ResultsConclusionFrequencies of cTfh cells were significantly increased in the peripheral blood of patients with IgG4-RD, and even higher frequencies were observed in the involved tissue. Percentages of programmed cell death protein 1 in CD4+CXCR5+ICOS+ cTfh cells were positively correlated with the serum levels of IgG and IgG4, IgG4:IgG ratio, number of involved organs, and frequency of CD19+CD24-CD38(high) plasmablasts/plasma cells. Levels of BLIMP-1 and IL-21 mRNA in peripheral CD4+ T cells were increased in patients with IgG4-RD compared to healthy controls, and this was correlated with the levels of serum IgG4. Moreover, in the involved tissue, Bcl-6, IL-21, and Tfh cells were highly expressed. Compared to cTfh cells from healthy controls, cTfh cells from patients with IgG4-RD could facilitate B cell proliferation and inhibit B cell apoptosis more efficiently, and enhanced the differentiation of naive B cells into switched memory B cells and plasmablasts/plasma cells, with a resultant increase in the secretion of IgG4. Notably, the cTfh1 and cTfh2 cell subsets were the most effective at providing B cell help.Tfh cell subsets are expanded in IgG4-RD and may play pivotal roles in the pathogenesis of the disease.