Trained immunity and tolerance in innate lymphoid cells, monocytes, and dendritic cells during allergen-specific immunotherapy,Journal of Allergy and Clinical Immunology

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Trained immunity and tolerance in innate lymphoid cells, monocytes, and dendritic cells during allergen-specific immunotherapy
Journal of Allergy and Clinical Immunology ( IF 11.4 ) Pub Date : 2020-10-09 , DOI: 10.1016/j.jaci.2020.08.042
Andrzej Eljaszewicz ₁ , Fiorella Ruchti ₂ , Urszula Radzikowska ₁ , Anna Globinska ₂ , Tadech Boonpiyathad ₃ , Anna Gschwend ₄ , Hideaki Morita ₅ , Arthur Helbling ₄ , Stefania Arasi ₆ , Helga Kahlert ₇ , Nadine Berek ₇ , Andreas Nandy ₇ , Mübeccel Akdis ₈ , Christoph Willers ₇ , Marcin Moniuszko ₉ , Cezmi A Akdis ₂ , Milena Sokolowska ₂

Affiliation

Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland.
Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand; Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
University Clinic for Rheumatology, Immunology and Allergology, Insel Hospital, University Hospital Bern, Bern, Switzerland.
Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland; Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland; Pediatric Allergology Unit, Department of Pediatric Medicine, Bambino Gesù Children's Research Hospital (IRCCS), Rome, Italy.
Allergopharma GmbH & Co KG, Reinbek, Germany.
Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland.
Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland; Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.

Background

Despite the efficacy of allergen-specific immunotherapy (AIT), the role of trained immunity and tolerance in this process has not been elucidated.

Objective

Here, we have performed a comprehensive longitudinal analysis of the systemic innate immune cell repertoire during the course of AIT.

Methods

Patients with allergy received standard preseasonal subcutaneous AIT with allergoids to birch and/or grass. Healthy controls were monitored without any intervention. Flow cytometry of innate lymphoid cell (ILC), natural killer cell, monocyte cell, and dendritic cell (DC) subsets was performed at baseline, 3 months (birch season), 6 months (grass seasons), and 12 months after the therapy in patients or at similar seasonal time points in controls. Additional analyses were performed in the third-year birch and grass season.

Results

We observed a durable decrease in group 2 ILCs and an increase of group 1 ILCs after AIT, with dynamic changes in their composition. We found that an expansion of CD127⁺CD25⁺⁺ clusters caused observed shifts in the heterogeneity of group 1 ILCs. In addition, we observed development of CD127⁺CD25⁺⁺c-Kit⁺ group 3 ILC clusters. Moreover, we found an increase in the number of intermediate monocytes in parallel with a reduction in nonclassical monocytes during the first year after AIT. Classical and intermediate monocytes presented significant heterogeneity in patients with allergy, but AIT reduced the HLA-DR⁺⁺ clusters. Finally, an increase in plasmacytoid DCs and CD141⁺ myeloid DCs was observed in individuals with allergy, whereas the number of CD1c⁺ myeloid DCs was reduced during the first year of AIT.

Conclusion

AIT induces changes in the composition and heterogeneity of circulating innate immune cells and brings them to the level observed in healthy individuals. Monitoring of ILCs, monocytes, and DCs during AIT might serve as a novel biomarker strategy.

中文翻译：

过敏原特异性免疫治疗期间先天淋巴细胞、单核细胞和树突状细胞的受过训练的免疫和耐受性

背景

尽管过敏原特异性免疫疗法 (AIT) 具有疗效，但尚未阐明训练有素的免疫和耐受性在该过程中的作用。

客观的

在这里，我们对 AIT 过程中的全身先天免疫细胞库进行了全面的纵向分析。

方法

过敏患者接受标准的季节性前皮下 AIT，其中含有对桦木和/或草的过敏原。在没有任何干预的情况下监测健康对照。先天淋巴细胞 (ILC)、自然杀伤细胞、单核细胞和树突状细胞 (DC) 亚群的流式细胞术在基线、3 个月（桦树季节）、6 个月（草季节）和治疗后 12 个月进行患者或对照组中类似的季节性时间点。在第三年的桦树和草地季节进行了额外的分析。

结果

我们观察到 AIT 后第 2 组 ILC 持续减少，第 1 组 ILC 增加，其组成发生动态变化。我们发现 CD127 ⁺ CD25 ⁺⁺簇的扩展导致观察到的第 1 组 ILC 异质性的变化。此外，我们观察到 CD127 ⁺ CD25 ⁺⁺ c-Kit ⁺第 3 组 ILC 簇的发展。此外，我们发现在 AIT 后的第一年，中间单核细胞数量增加，非经典单核细胞减少。经典和中间单核细胞在过敏患者中表现出显着的异质性，但 AIT 减少了 HLA-DR ⁺⁺簇。最后，浆细胞样 DC 和 CD141 ⁺在过敏个体中观察到髓样 DCs，而在AIT 的第一年中CD1c ⁺髓样 DCs的数量减少。