دورية أكاديمية
Widespread alterations in systemic immune profile are linked to lung function heterogeneity and airway microbes in cystic fibrosis.
| العنوان: | Widespread alterations in systemic immune profile are linked to lung function heterogeneity and airway microbes in cystic fibrosis. |
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| المؤلفون: | Rossi E; Department of Clinical Microbiology, Rigshospitalet, Copenhagen Ø, Denmark; Department of Biosciences, University of Milan, Milan, Italy. Electronic address: elio.rossi@unimi.it., Lausen M; Department of Clinical Microbiology, Rigshospitalet, Copenhagen Ø, Denmark., Øbro NF; Department of Clinical Immunology, Rigshospitalet, Copenhagen Ø, Denmark., Colque CA; Department of Clinical Microbiology, Rigshospitalet, Copenhagen Ø, Denmark., Nielsen BU; Department of Infectious Diseases, Rigshospitalet, Cystic Fibrosis Centre, Copenhagen Ø, Denmark., Møller R; Department of Infectious Diseases, Rigshospitalet, Cystic Fibrosis Centre, Copenhagen Ø, Denmark., de Gier C; Department of Clinical Microbiology, Rigshospitalet, Copenhagen Ø, Denmark., Hald A; Department of Infectious Diseases, Rigshospitalet, Cystic Fibrosis Centre, Copenhagen Ø, Denmark., Skov M; Department of Pediatrics, Rigshospitalet, Cystic Fibrosis Centre, Copenhagen, Denmark., Pressler T; Department of Infectious Diseases, Rigshospitalet, Cystic Fibrosis Centre, Copenhagen Ø, Denmark; Department of Pediatrics, Rigshospitalet, Cystic Fibrosis Centre, Copenhagen, Denmark., Ostrowski SR; Department of Clinical Immunology, Rigshospitalet, Copenhagen Ø, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark., Marquart HV; Department of Clinical Immunology, Rigshospitalet, Copenhagen Ø, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark., Johansen HK; Department of Clinical Microbiology, Rigshospitalet, Copenhagen Ø, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark. |
| المصدر: | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society [J Cyst Fibros] 2024 Sep; Vol. 23 (5), pp. 885-895. Date of Electronic Publication: 2024 May 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101128966 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5010 (Electronic) Linking ISSN: 15691993 NLM ISO Abbreviation: J Cyst Fibros Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier, c2002- |
| مواضيع طبية MeSH: | Cystic Fibrosis*/microbiology , Cystic Fibrosis*/immunology , Sputum*/microbiology , Sputum*/immunology , Microbiota*/immunology, Humans ; Male ; Female ; Lung/immunology ; Lung/microbiology ; Adult ; Respiratory Function Tests/methods ; Flow Cytometry |
| مستخلص: | Background: Excessive inflammation and recurrent airway infections characterize people with cystic fibrosis (pwCF), a disease with highly heterogeneous clinical outcomes. How the overall immune response is affected in pwCF, its relationships with the lung microbiome, and the source of clinical heterogeneity have not been fully elucidated. Methods: Peripheral blood and sputum samples were collected from 28 pwCF and an age-matched control group. Systemic immune cell subsets and surface markers were quantified using multiparameter flow cytometry. Lung microbiome composition was reconstructed using metatranscriptomics on sputum samples, and microbial taxa were correlated to circulating immune cells and surface markers expression. Results: In pwCF, we found a specific systemic immune profile characterized by widespread hyperactivation and altered frequencies of several subsets. These included substantial changes in B-cell subsets, enrichment of CD35 + /CD49d + neutrophils, and reduction in dendritic cells. Activation markers and checkpoint molecule expression levels differed from healthy subjects. CTLA-4 expression was increased in Tregs and, together with impaired B-cell subsets, correlated with patients' lung function. Concentrations and frequencies of key immune cells and marker expression correlated with the relative abundance of commensal and pathogenic bacteria in the lungs. Conclusion: The CF-specific immune signature, involving hyperactivation, immune dysregulation with alteration in Treg homeostasis, and impaired B-cell function, is a potential source of lung function heterogeneity. The activity of specific microbes contributes to disrupting the balance of the immune response. Our data provide a unique foundation for identifying novel markers and immunomodulatory targets to develop the future of cystic fibrosis treatment and management. Competing Interests: Declaration of competing interest We declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Adaptive immunity; Cystic fibrosis; Immune dysregulation; Infections; Innate immunity; Lung microbiome |
| تواريخ الأحداث: | Date Created: 20240503 Date Completed: 20240918 Latest Revision: 20240918 |
| رمز التحديث: | 20240919 |
| DOI: | 10.1016/j.jcf.2024.04.015 |
| PMID: | 38702223 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1873-5010 |
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| DOI: | 10.1016/j.jcf.2024.04.015 |