Immunoglobulin A Mucosal Immunity and Altered Respiratory Epithelium in Cystic Fibrosis

Gohy, Sophie; Moeremans, Alexandra; Pilette, Charles; Collin, Amandine

doi:10.3390/cells10123603

Cited by 11 publications

(12 citation statements)

References 133 publications

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“…Concurrently SIgA production and transcytosis was shown to be upregulated through IL-17 induced by chronic Pseudomonas aeruginosa infection. In addition increased amounts of dysfunctional SC were observed in sputum of CF patients ( 2 , 23 , 37 ). In summary, the interplay between multiple components affects the pIgR/SIgA axis and induces the dysregulated mucosal immunity in CF.…”

Section: Iga In Inflammatory Lung Diseasesmentioning

confidence: 99%

“…A harmful circle of neutrophil-mediated inflammation and impaired SIgA function potentiates chronic inflammation and recurrent infections. The role of neutrophils is dually detrimental in the observed pathology as the released inflammatory mediators can mediate tissue damage, increase inflammation and some, especially neutrophil elastase and proteinase-3, can degrade pIgR, SC and mucosa immunoglobulins ( 1 , 23 , 53 , 54 ). Therefore, the regulation of neutrophil inflammation could be a valuable therapeutic strategy.…”

Section: Iga In Inflammatory Lung Diseasesmentioning

confidence: 99%

“…Based on transgenic mouse and in vitro studies, SIgA binding can promote inflammatory activation of the mucosal immune response e.g. phagocytosis, ADCC, ROS generation, degranulation and inflammatory cytokine secretion ( 1 , 2 , 23 , 51 , 74 ). Furthermore, the binding of SIgA opsonized pathogens to FcαRI on neutrophils, induces LTB4-release and recruitment of further neutrophils to the lung ( Figure 1C ) ( 87 , 89 ).…”

Section: The Functional Role Of Igamentioning

confidence: 99%

“…After translocation, a part of the pIgR, called secretory component (SC), remains attached to IgA and thereby forms the secretory IgA (SIgA) ( 13 , 22 ). The SC stabilizes the SIgA molecule and protects it from proteolytic degradation ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

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A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Bohländer

2023

Front. Immunol.

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Inflammatory lung diseases represent a persistent burden for patients and the global healthcare system. The combination of high morbidity, (partially) high mortality and limited innovations in the last decades, have resulted in a great demand for new therapeutics. Are therapeutic IgA antibodies possibly a new hope in the treatment of inflammatory lung diseases? Current research increasingly unravels the elementary functions of IgA as protector against infections and as modulator of overwhelming inflammation. With a focus on IgA, this review describes the pathological alterations in mucosal immunity and how they contribute to chronic inflammation in the most common inflammatory lung diseases. The current knowledge of IgA functions in the circulation, and particularly in the respiratory mucosa, are summarized. The interplay between neutrophils and IgA seems to be key in control of inflammation. In addition, the hurdles and benefits of therapeutic IgA antibodies, as well as the currently known clinically used IgA preparations are described. The data highlighted here, together with upcoming research strategies aiming at circumventing the current pitfalls in IgA research may pave the way for this promising antibody class in the application of inflammatory lung diseases.

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Section: Iga In Inflammatory Lung Diseasesmentioning

confidence: 99%

Section: Iga In Inflammatory Lung Diseasesmentioning

confidence: 99%

Section: The Functional Role Of Igamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Bohländer

2023

Front. Immunol.

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“…A further evidence of the complex interplay between microenvironment and host regulation of epithelial pIgR expression is coming from studies in CF, where our group showed that in the dedifferentiated lower airway epithelium ( 135 ), the intrinsic downregulation of pIgR expression seen upon CFTR dysfunction, is upregulated and overcome in vivo , likely as a result of the presence of opportunistic bacteria such as P. aeruginosa ( 69 ). IgA immunity in CF was recently reviewed in details ( 136 ).…”

Section: Role Of Iga In Lower Airway Diseasementioning

confidence: 99%

The Role of IgA in Chronic Upper Airway Disease: Friend or Foe?

et al. 2022

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Chronic upper airway inflammation is amongst the most prevalent chronic disease entities in the Western world with prevalence around 30% (rhinitis) and 11% (rhinosinusitis). Chronic rhinitis and rhinosinusitis may severely impair the quality of life, leading to a significant socio-economic burden. It becomes more and more clear that the respiratory mucosa which forms a physiological as well as chemical barrier for inhaled particles, plays a key role in maintaining homeostasis and driving disease. In a healthy state, the mucosal immune system provides protection against pathogens as well as maintains a tolerance toward non-harmful commensal microbes and benign environmental substances such as allergens. One of the most important players of the mucosal immune system is immunoglobulin (Ig) A, which is well-studied in gut research where it has emerged as a key factor in creating tolerance to potential food allergens and maintaining a healthy microbiome. Although, it is very likely that IgA plays a similar role at the level of the respiratory epithelium, very little research has been performed on the role of this protein in the airways, especially in chronic upper airway diseases. This review summarizes what is known about IgA in upper airway homeostasis, as well as in rhinitis and rhinosinusitis, including current and possible new treatments that may interfere with the IgA system. By doing so, we identify unmet needs in exploring the different roles of IgA in the upper airways required to find new biomarkers or therapeutic options for treating chronic rhinitis and rhinosinusitis.

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Pathogenesis of nontypeable Haemophilus influenzae infections in chronic suppurative lung disease

Chatziparasidis

Kantar

Grimwood

2023

Pediatric Pulmonology

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The respiratory tract antimicrobial defense system is a multilayered defense mechanism that relies upon mucociliary clearance and components of both the innate and adaptive immune systems to protect the lungs from inhaled or aspirated microorganisms. One of these potential pathogens, nontypeable Haemophilus influenzae (NTHi), adopts several, multifaceted redundant strategies to successfully colonize the lower airways and establish a persistent infection. NTHi can impair mucociliary clearance, express multiple multifunctional adhesins for various cell types within the respiratory tract and evade host defenses by surviving within and between cells, forming biofilms, increasing antigenic drift, secreting proteases and antioxidants, and by host‐pathogen cross‐talk, impair macrophage and neutrophil function. NTHi is recognized as an important pathogen in several chronic lower respiratory disorders, such as protracted bacterial bronchitis, bronchiectasis, cystic fibrosis, and primary ciliary dyskinesia. The persistence of NTHi in human airways, including its capacity to form biofilms, results in chronic infection and inflammation, which can ultimately injure airway wall structures. The complex nature of the molecular pathogenetic mechanisms employed by NTHi is incompletely understood but improved understanding of its pathobiology will be important for developing effective therapies and vaccines, especially given the marked genetic heterogeneity of NTHi and its possession of phase‐variable genes. Currently, no vaccine candidates are ready for large phase III clinical trials.

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Immunoglobulin A Mucosal Immunity and Altered Respiratory Epithelium in Cystic Fibrosis

Cited by 11 publications

References 133 publications

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

The Role of IgA in Chronic Upper Airway Disease: Friend or Foe?

Pathogenesis of nontypeable Haemophilus influenzae infections in chronic suppurative lung disease

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