Aberrant populations of circulating T follicular helper cells and regulatory B cells underlying idiopathic pulmonary fibrosis
Aberrant populations of circulating T follicular helper cells and regulatory B cells underlying idiopathic pulmonary fibrosis
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DOI：
10.1186/s12931-019-1216-6
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发表时间：
2019-11-06
影响因子：
5.8
通讯作者：
Takahashi, Hiroki
中科院分区：
文献类型：
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作者：
Asai, Yuichiro;Chiba, Hirofumi;Takahashi, Hiroki
研究背景滤泡辅助性T细胞（Tfh）是一类新发现的辅助性T细胞，其表面表达CXCR 5并诱导抗原特异性抗体的产生。许多研究已经发现Tfh细胞在系统性自身免疫和变应性疾病中的病态增殖和/或活化。还已知在恶化的这类疾病中Tfh细胞受调节性B（布雷格）细胞调节。最近，CXCL 13，CXCR 5的配体，已被报道在特发性肺纤维化（IPF）患者的外周血和肺中增加。本研究旨在研究Tfh细胞和布雷格细胞在IPF中的参与。方法收集18例IPF患者的外周血标本。我们分离肝素化的外周血单个核细胞，并通过流式细胞术研究布雷格细胞、Tfh细胞、PD-1（+）ICOS（+）Tfh细胞（Tfh细胞的活化形式）和Tfh-细胞亚群的比例。将这些细胞谱与21名健康对照者的细胞谱进行比较。此外，我们研究了淋巴细胞和肺生理学之间的相关性。结果IPF患者中Tfh细胞占总CD 4（+）T细胞的中位比例和PD-1（+）ICOS（+）Tfh细胞占总Tfh细胞的中位比例（分别为20.4%和5.2%）显著高于健康对照组（分别为15.4%和2.1%;分别为p = 0.042和p = 0.004）。与健康对照组相比，IPF患者中Tfh 2细胞/总Tfh细胞的比例显著较高，Tfh 17的比例较小。与对照组相比，IPF患者中布雷格细胞占总B细胞的百分比（中位数，8.5%）显著降低（中位数，19.7%; p < 0.001）。布雷格细胞比例与IPF患者肺一氧化碳弥散量的年相对变化呈正相关（r = 0.583，p = 0.018）。结论IPF患者外周血中存在Tfh细胞增殖活化和布雷格细胞减少。Tfh细胞亚群的分布也发生了变化。特异性体液免疫异常可能是IPF复杂病理生理学的基础。
Background T follicular helper (Tfh) cells have been identified as a new category of helper T cells, which express CXCR5 on their surface and induce the production of antigen-specific antibodies. Many investigations have found morbid proliferation and/or activation of Tfh cells in systemic autoimmune and allergic diseases. It is also known that Tfh cells are regulated by regulatory B (Breg) cells in the deteriorating such diseases. Recently, CXCL13, a ligand of CXCR5, has been reported to increase in the peripheral blood and lungs of patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the involvement of Tfh cells and Breg cells in IPF. Methods Peripheral blood samples were obtained from 18 patients with IPF. We isolated heparinized peripheral blood mononuclear cells and investigated the proportions of Breg cells, Tfh cells, PD-1(+)ICOS(+) Tfh cells (activated form of Tfh cells), and the Tfh-cell subsets by flow cytometry. These cell profiles were compared with those of 21 healthy controls. Furthermore, we investigated the correlations between profiles of lymphocytes and lung physiology. Results The median proportions of Tfh cells per total CD4(+) T cells and of PD-1(+)ICOS(+) proportion of Tfh cells per total Tfh cells was significantly more in the IPF patients (20.4 and 5.2%, respectively) compared with healthy controls (15.4 and 2.1%, respectively; p = 0.042 and p = 0.004, respectively). The proportion of Tfh2 cells per total Tfh cells was significantly higher and the proportion of Tfh17 was smaller in the IPF patients than healthy controls. The percentage of Breg cells to total B cells was significantly decreased in the IPF patients (median, 8.5%) compared with that in the controls (median, 19.7%; p < 0.001). The proportion of Breg cells was positively correlated with the annual relative change in diffusing capacity of the lungs for carbon monoxide in the IPF patients (r = 0.583, p = 0.018). Conclusion Proliferation and activation of Tfh cells and a decrease in Breg cells were observed in the peripheral blood of patients with IPF. The profile of the Tfh-cell subset also changed. Specific humoral immunity aberration would likely underlie complicated pathophysiology of IPF.