Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy,Journal of Allergy and Clinical Immunology

当前位置： X-MOL 学术 › J. Allergy Clin. Immunol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy
Journal of Allergy and Clinical Immunology ( IF 11.4 ) Pub Date : 2020-11-06 , DOI: 10.1016/j.jaci.2020.10.035
Hanisah Sharif ₁ , Swati Acharya ₂ , Gopal Krishna R Dhondalay ₂ , Gilda Varricchi ₃ , Shoshanna Krasner-Macleod ₄ , Wannada Laisuan ₅ , Amy Switzer ₄ , Madison Lenormand ₅ , Elena Kashe ₄ , Rebecca V Parkin ₅ , Yi Yi ₅ , Merve Koc ₅ , Oleksandra Fedina ₄ , Gemma Vilà-Nadal ₄ , Gianni Marone ₆ , Aarif Eifan ₄ , Guy W Scadding ₄ , David J Fear ₇ , Kari C Nadeau ₂ , Stephen R Durham ₄ , Mohamed H Shamji ₅

Affiliation

Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, London, United Kingdom; Asthma UK Centre in Allergic Mechanisms of Asthma, London, Imperial College London, London, United Kingdom; PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Gadong, Brunei Darussalam.
Sean N. Parker Center for Asthma and Allergy Research, Department of Medicine, Stanford University, Stanford, Calif.
Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, London, United Kingdom; Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, London, United Kingdom.
Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, London, United Kingdom; Asthma UK Centre in Allergic Mechanisms of Asthma, London, Imperial College London, London, United Kingdom.
Division of Clinical Immunology and Allergy, Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Asthma UK Centre in Allergic Mechanisms of Asthma, Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London, United Kingdom.

Background

Allergen-specific immunotherapy is a disease-modifying treatment that induces long-term T-cell tolerance.

Objective

We sought to evaluate the role of circulating CXCR5⁺PD-1⁺ T follicular helper (cT_FH) and T follicular regulatory (T_FR) cells following grass pollen subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) and the accompanying changes in their chromatin landscape.

Methods

Phenotype and function of cT_FH cells were initially evaluated in the grass pollen-allergic (GPA) group (n = 28) and nonatopic healthy controls (NAC, n = 13) by mathematical algorithms developed to manage high-dimensional data and cell culture, respectively. cT_FH and T_FR cells were further enumerated in NAC (n = 12), GPA (n = 14), SCIT- (n = 10), and SLIT- (n = 8) treated groups. Chromatin accessibility in cT_FH and T_FR cells was assessed by assay for transposase-accessible chromatin sequencing (ATAC-seq) to investigate epigenetic mechanisms underlying the differences between NAC, GPA, SCIT, and SLIT groups.

Results

cT_FH cells were shown to be distinct from T_H2- and T_H2A-cell subsets, capable of secreting IL-4 and IL-21. Both cytokines synergistically promoted B-cell class switching to IgE and plasma cell differentiation. Grass pollen allergen induced cT_FH-cell proliferation in the GPA group but not in the NAC group (P < .05). cT_FH cells were higher in the GPA group compared with the NAC group and were lower in the SCIT and SLIT groups (P < .01). Time-dependent induction of IL-4, IL-21, and IL-6 was observed in nasal mucosa following intranasal allergen challenge in the GPA group but not in SCIT and SLIT groups. T_FR and IL-10⁺ cT_FH cells were induced in SCIT and SLIT groups (all, P < .01). ATAC-seq analyses revealed differentially accessible chromatin regions in all groups.

Conclusions

For the first time, we showed dysregulation of cT_FH cells in the GPA group compared to NAC, SCIT, and SLIT groups and induction of T_FR and IL-10⁺ cT_FH cells following SCIT and SLIT. Changes in the chromatin landscape were observed following allergen-specific immunotherapy in cT_FH and T_FR cells.

中文翻译：

草花粉皮下和舌下免疫治疗后循环 T 滤泡辅助细胞和调节细胞的染色质景观改变

背景

过敏原特异性免疫疗法是一种改善疾病的治疗方法，可诱导长期 T 细胞耐受。

客观的

我们试图评估草花粉皮下免疫治疗 (SCIT) 和舌下免疫治疗 (SLIT)后循环 CXCR5 ⁺ PD-1 ⁺ T 滤泡辅助 (cT _FH ) 和 T 滤泡调节 (T _FR ) 细胞的作用及其伴随的变化。染色质景观。

方法

最初通过为管理高维数据和细胞培养而开发的数学算法在草花粉过敏 (GPA) 组 (n = 28) 和非特应性健康对照 (NAC, n = 13) 中评估了 cT _FH细胞的表型和功能，分别。在 NAC (n = 12)、GPA (n = 14)、SCIT- (n = 10) 和 SLIT- (n = 8) 治疗组中进一步列举了cT _FH和 T _FR细胞。cT _FH和 T _FR细胞中的染色质可及性通过测定转座酶可及染色质测序 (ATAC-seq) 进行评估，以研究 NAC、GPA、SCIT 和 SLIT 组之间差异的表观遗传机制。

结果

显示 cT _FH细胞不同于 T _H 2 和 T _H 2A 细胞亚群，能够分泌 IL-4 和 IL-21。两种细胞因子协同促进 B 细胞类别转换为 IgE 和浆细胞分化。草花粉过敏原在 GPA 组中诱导 cT _FH细胞增殖，但在 NAC 组中不诱导( P < .05)。与 NAC 组相比，GPA 组的cT _FH细胞较高，而 SCIT 和 SLIT 组的cT _FH细胞较低 ( P < .01)。在 GPA 组鼻内过敏原攻击后，在鼻粘膜中观察到 IL-4、IL-21 和 IL-6 的时间依赖性诱导，但在 SCIT 和 SLIT 组中未观察到。T _FR和 IL-10 ⁺在 SCIT 和 SLIT 组中诱导cT _FH细胞（所有，P < .01）。ATAC-seq 分析揭示了所有组中不同可及的染色质区域。