Imbalance in B cell and T Follicular Helper Cell Subsets in Pulmonary Sarcoidosis
Imbalance in B cell and T Follicular Helper Cell Subsets in Pulmonary Sarcoidosis
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DOI：
10.1038/s41598-020-57741-0
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发表时间：
2020-01-23
影响因子：
4.6
通讯作者：
Shoenfeld, Y.
中科院分区：
文献类型：
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作者：
Kudryavtsev, I.;Serebriakova, M.;Shoenfeld, Y.
结节病是一种由于 Th1、Th17 和 Treg 淋巴细胞紊乱而发生的全身性肉芽肿性疾病。有一种假设认为，B 细胞和滤泡 T 辅助细胞 (Tfh) 可能在这种疾病以及其他几种自身免疫性疾病中发挥重要作用。本研究的目的是确定结节病患者外周血中 CD19+ B 细胞亚群的分布，并确定循环 Tfh 细胞亚群的紊乱。这项前瞻性比较研究于 2016-2018 年进行，使用多色流式细胞术对 37 名初诊结节病患者和 35 名健康供者的外周血 B 细胞亚群和循环 Tfh 细胞亚群进行了分析。在我们的研究结果中，我们发现结节病患者外周血中外周 B 细胞亚群的分布发生了改变，其中以“初始”（IgD + CD27-）和活化 B 细胞（Bm2 和 Bm2'）亚群为主，并且记忆细胞（IgD+ CD27+ 和 IgD- CD27+）频率降低。此外，我们发现结节病患者的 B 细胞亚群水平升高，此前已证明这些 B 细胞亚群具有调节能力（CD24+++ CD38+++ 和 CD5 + CD27-）。接下来，与健康对照相比，结节病患者中表达 CXCR5 的 CD45RA - CCR7+ Th 细胞的比例显着更高，这代表了该疾病中这种记忆 Th 细胞亚群的扩张。这是第一项证明结节病的发展与循环 Tfh 细胞（尤其是表达 CCR4 和 CXCR3 的 Tfh 亚群）失衡之间关联的研究。最后，根据我们的数据，我们可以假设 B 细胞以及 Tfh2 和 Tfh17 样细胞（支持 B 细胞活性（特别是抗体生成）最有效的细胞类型）可能参与结节病和其他几种自身免疫性疾病的发生和发展。因此，我们可以将这些结果视为结节病发展中自身免疫机制的新证据。
Sarcoidosis is a systemic granulomatous disease that develops due to the Th1, Th17 and Treg lymphocytes disturbance. There is an assumption, that B cells and follicular T-helper (Tfh) cells may play an important role in this disorder, as well as in several other autoimmune diseases. The aim of this study was to determine CD19+ B cells subset distribution in the peripheral blood and to define disturbance in the circulating Tfh cells subsets in patients with sarcoidosis. The prospective comparative study was performed in 2016-2018, where peripheral blood B cell subsets and circulating Tfh cell subsets were analyzed in 37 patients with primarily diagnosed sarcoidosis and 35 healthy donors using multicolor flow cytometry. In the results of our study we found the altered distribution of peripheral B cell subsets with a predominance of "naive" (IgD + CD27-) and activated B cell (Bm2 and Bm2') subsets and a decreased frequency of memory cell (IgD+ CD27+ and IgD- CD27+) in peripheral blood of sarcoidosis patients was demonstrated. Moreover, we found that in sarcoidosis patients there are increased levels of B cell subsets, which were previously shown to display regulatory capacities (CD24+++ CD38+++ and CD5 + CD27-). Next, a significantly higher proportion of CXCR5-expressing CD45RA - CCR7+ Th cells in patients with sarcoidosis in comparison to the healthy controls was revealed, that represents the expansion of this memory Th cell subset in the disease. This is the first study to demonstrate the association between the development of sarcoidosis and imbalance of circulating Tfh cells, especially CCR4- and CXCR3-expressing Tfh subsets. Finally, based on our data we can assume that B cells and Tfh2- and Tfh17-like cells - most effective cell type in supporting B-cell activity, particularly in antibody production - may be involved in the occurrence and development of sarcoidosis and in several other autoimmune conditions. Therefore, we can consider these results as a new evidence of the autoimmune mechanisms in the sarcoidosis development.