PDF(Pubmed)
Abstract：
BACKGROUND: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear.
METHODS: We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21+CD4+T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4+T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures in vitro were measured.
RESULTS: ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T-cells were mainly peripheral T-helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE.
CONCLUSIONS: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.
METHODS: We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21+CD4+T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4+T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures in vitro were measured.
RESULTS: ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T-cells were mainly peripheral T-helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE.
CONCLUSIONS: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.
摘要：
背景：过敏性支气管肺曲霉病（ABPA）患者反复加重。然而,T细胞亚群的参与仍不清楚.
方法：我们招募了ABPA患者，哮喘患者和健康对照。通过流式细胞术分析外周血单个核细胞（PBMC）和ABPA支气管肺泡灌洗液（BALF）的总或分选亚群中的Th1，Th2，Th17，Treg和IL-21CD4T细胞。在恶化的ABPA患者和健康对照中进行CD4+T细胞亚群的RNA测序。测量体外T-B细胞共培养物的抗体。
结果：ABPA患者Th2细胞增多，Treg细胞相似，循环Th1和Th17细胞减少。IL-5+IL-13+IL-21+CD4+T细胞在健康对照组中很少检测到，但在ABPA患者的血液中显著升高，尤其是加剧的。我们发现IL-5+IL-13+IL-21+CD4+T细胞主要是外周辅助性T（Tph）细胞（PD-1+CXCR5-），也出现在ABPA患者的BALF中。ABPA患者中循环Tph的比例相似，哮喘患者和健康对照，而IL-5+IL-13+IL-21+Tph细胞在ABPA患者中显著增加。转录组数据显示ABPA患者的Tph细胞是Th2偏斜的，并表现出滤泡性T辅助细胞（Tfh）的特征。体外共培养时，ABPA患者的Tph细胞诱导自体B细胞分化为成浆细胞，并显着增强IgE的产生。
结论：我们确定了在ABPA患者中诱导IgE产生的循环Th2偏斜Tph细胞群明显升高。它可能是ABPA的生物标志物和治疗靶标。
方法：我们招募了ABPA患者，哮喘患者和健康对照。通过流式细胞术分析外周血单个核细胞（PBMC）和ABPA支气管肺泡灌洗液（BALF）的总或分选亚群中的Th1，Th2，Th17，Treg和IL-21CD4T细胞。在恶化的ABPA患者和健康对照中进行CD4+T细胞亚群的RNA测序。测量体外T-B细胞共培养物的抗体。
结果：ABPA患者Th2细胞增多，Treg细胞相似，循环Th1和Th17细胞减少。IL-5+IL-13+IL-21+CD4+T细胞在健康对照组中很少检测到，但在ABPA患者的血液中显著升高，尤其是加剧的。我们发现IL-5+IL-13+IL-21+CD4+T细胞主要是外周辅助性T（Tph）细胞（PD-1+CXCR5-），也出现在ABPA患者的BALF中。ABPA患者中循环Tph的比例相似，哮喘患者和健康对照，而IL-5+IL-13+IL-21+Tph细胞在ABPA患者中显著增加。转录组数据显示ABPA患者的Tph细胞是Th2偏斜的，并表现出滤泡性T辅助细胞（Tfh）的特征。体外共培养时，ABPA患者的Tph细胞诱导自体B细胞分化为成浆细胞，并显着增强IgE的产生。
结论：我们确定了在ABPA患者中诱导IgE产生的循环Th2偏斜Tph细胞群明显升高。它可能是ABPA的生物标志物和治疗靶标。
