Widespread alterations in systemic immune profile are linked to lung function heterogeneity and airway microbes in cystic fibrosis
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Widespread alterations in systemic immune profile are linked to lung function heterogeneity and airway microbes in cystic fibrosis. / Rossi, Elio; Lausen, Mads; Øbro, Nina Friesgaard; Colque, Antonella; Nielsen, Bibi Uhre; Møller, Rikke; de Gier, Camilla; Hald, Annemette; Skov, Marianne; Pressler, Tacjana; Molin, Søren; Ostrowski, Sisse Rye; Marquart, Hanne Vibeke; Johansen, Helle Krogh.
I: Journal of Cystic Fibrosis, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Widespread alterations in systemic immune profile are linked to lung function heterogeneity and airway microbes in cystic fibrosis
AU - Rossi, Elio
AU - Lausen, Mads
AU - Øbro, Nina Friesgaard
AU - Colque, Antonella
AU - Nielsen, Bibi Uhre
AU - Møller, Rikke
AU - de Gier, Camilla
AU - Hald, Annemette
AU - Skov, Marianne
AU - Pressler, Tacjana
AU - Molin, Søren
AU - Ostrowski, Sisse Rye
AU - Marquart, Hanne Vibeke
AU - Johansen, Helle Krogh
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Adaptive immunity
KW - Cystic fibrosis
KW - Immune dysregulation
KW - Infections
KW - Innate immunity
KW - Lung microbiome
U2 - 10.1016/j.jcf.2024.04.015
DO - 10.1016/j.jcf.2024.04.015
M3 - Journal article
C2 - 38702223
AN - SCOPUS:85191943896
JO - Journal of Cystic Fibrosis
JF - Journal of Cystic Fibrosis
SN - 1569-1993
ER -
ID: 393135646