Widespread alterations in systemic immune profile are linked to lung function heterogeneity and airway microbes in cystic fibrosis
Articolo
Data di Pubblicazione:
2024
Citazione:
Widespread alterations in systemic immune profile are linked to lung function heterogeneity and airway microbes in cystic fibrosis / E. Rossi, M. Lausen, N. Friesgaard Øbro, A. Colque, B. Uhre Nielsen, R. Møller, C. de Gier, A. Hald, M. Skov, T. Pressler, S. Molin, S. Rye Ostrowski, H. Vibeke Marquart, H. Krogh Johansen. - In: JOURNAL OF CYSTIC FIBROSIS. - ISSN 1873-5010. - (2024 May), pp. 1-11. [10.1016/j.jcf.2024.04.015]
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Adaptive immunity; Cystic fibrosis; Immune dysregulation; Infections; Innate immunity; Lung microbiome
Elenco autori:
E. Rossi, M. Lausen, N. Friesgaard Øbro, A. Colque, B. Uhre Nielsen, R. Møller, C. de Gier, A. Hald, M. Skov, T. Pressler, S. Molin, S. Rye Ostrowski, H. Vibeke Marquart, H. Krogh Johansen
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