Current concepts of immune dysregulation in cystic fibrosis☆
Section snippets
Immunity in cystic fibrosis: more questions than answers
Cystic fibrosis (CF) lung disease is characterized by a chronic and non-resolving activation of the innate immune system with release of chemokines and an infiltration of neutrophils into the airways. Neutrophil-derived oxidants and proteases cause harm to multiple cellular and humoral factors and have recently been shown to impair Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) functionality itself (Le Gars et al., 2013). Beyond neutrophils, the immune response in CF lungs is
CFTR in myeloid cells
Previous studies provided convincing evidence that human neutrophils express the CFTR protein, localized in the membrane of secretory vesicles (Painter et al., 2006). Optimal microbicidal activity of neutrophils relies on the generation of toxic agents such as hypochlorous acid (HOCl) within phagosomes (Hampton et al., 1998). HOCl formation, in turn, requires chloride ion transported from the cytoplasm into phagosomes mediated by chloride channels (Nauseef, 2007). Studies demonstrated that
Immunity in cystic fibrosis: future directions
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Functional role of CFTR in myeloid cells: As several myeloid cells have been demonstrated to express CFTR protein (macrophages, neutrophils, and dendritic cells) and CFTR modulators are used nowadays for the treatment of CF patients with G551D mutations (Hoffman and Ramsey, 2013), their effect, particularly of the CFTR potentiator Ivacaftor (Kalydeco), on the homeostasis and functionality of myeloid cells remains to be defined.
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Homologies between the porcine and human immune system: The more
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Cited by (42)
Frequencies of pathogenic CFTR variants in Greek cystic fibrosis patients with allergic bronchopulmonary aspergillosis and Aspergillus fumigatus chronic colonization: A retrospective cohort study
2023, Journal of Medical MycologyCitation Excerpt :However, the relationship between CFTR genotype and the clinical spectrum of A. fumigatus in CF has not been fully clarified yet. It is well known that CFTR is expressed in cells of both the innate and adaptive immune system and seems to play a critical role in their function [5]. According to Chaudhary et al., epithelial cells in CFTR/murine models expressed defective clearance of A. fumigatus conidia and increased susceptibility to apoptosis [6].
The effect of the cystic fibrosis care center on outcomes after lung transplantation for cystic fibrosis
2022, Journal of Heart and Lung TransplantationCitation Excerpt :Accreditation as a CFCC is based on the determination by the CFF that a center is able to provide specialized care for CF patients, and meets published best practices including structures of care for frequent complications and comorbidities of CF. For example, there are guidelines for pulmonary care and infection control as well as requirements for colorectal cancer screening and nutritional support given the wide array of gastrointestinal manifestations of CF.3 The CFF performs routine site visits of CFCCs in order for centers to maintain accreditation. These requirements for comprehensive care that extend well beyond pulmonary medicine are especially important in CF as it is a chronic systemic disease with broad extra-pulmonary manifestations, with particular gastrointestinal, endocrine and infectious complications.2,4,26,30-33 Lung transplantation serves as a therapy for pulmonary failure in CF but does not address the systemic manifestations.
Therapeutic potential for coxibs-nitric oxide releasing hybrids in cystic fibrosis
2021, European Journal of Medicinal ChemistryCitation Excerpt :It was recently shown, how the reduction of COX protein levels (mainly COX-2) had a positive effect on all analysed clinical parameters. This suggests an important role of the inhibition of arachidonic acid conversion into prostaglandins which, by reducing the inflammatory process, acts as protective modifier of pulmonary disease in CF patients [17,18]. With the recognition that airway inflammation plays a significant pathogenic role in CF, modulation of the inflammatory response has become a significant therapeutic target and drugs that target inflammation have been shown to slow the decline in lung function and improve survival [19,20].
Pathophysiology of Cystic Fibrosis Liver Disease: A Channelopathy Leading to Alterations in Innate Immunity and in Microbiota
2019, Cellular and Molecular Gastroenterology and HepatologyAspergillus infections in cystic fibrosis
2016, Journal of InfectionCitation Excerpt :The pathophysiology of Aspergillus infections in the CF-lung, except for ABPA,48 is not known and the consequences of the absence of a functional CFTR protein on the specific host–fungus interaction is not understood. CFTR protein has been found in cells of both the innate and adaptive immune system49,50 and has shown to play a critical role for their normal function.51 Cystic fibrosis lung disease is characterized by early, non-resolving activation of the innate immune system, with excessive neutrophil recruitment followed by excessive expansion of lymphocyte populations and failure of normal counter-regulatory mechanisms.5,52
Modeling immunity in microphysiological systems
2023, Experimental Biology and Medicine
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This article is part of a Directed Issue entitled: Cystic Fibrosis: From o-mics to cell biology, physiology, and therapeutic advances.