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Project

Impaired secretory IgA production in chronic rhinosinusitis: role and regulatory mechanisms

Chronic Rhinosinusitis (CRS) represents a very frequent disease with an enormous impact on quality of life and work loss in our society. So far, its pathophysiology remains rather unclear and nothing is known about the role of immunoglobulin A (IgA), a protective antibody that seems to be dysfunctional in these patients. To study the role of IgA and its polymeric Ig receptor (pIgR) in vivo, we will test 3 models of different CRS phenotypes (eosinophilic, neutrophilic and infectious) that correspond to the human phenotypes in wild type mice and compare them to mice that lack IgA or pIgR. Secondly, we will obtain nasal secretions from CRS patients and controls and investigate the interaction between IgA and members of the sinonasal microbiome. This will be done via flow cytometry-based bacterial cell sorting and 16S sequencing to characterize taxa-specific coating of the microbiota with IgA (IgA−SEQ). According to the results, IgA+ and IgA- members of the human microbiome will be administered intranasally into the nostrils of germ-free mice in order to evaluate their direct ‘sinusitogenic’ capacity. To identify the cause of the IgA dysfunction witnessed in CRS, we investigate whether primary cultured nasal epithelial cells from CRS patients express less pIgR than controls and whether this is due to a reprogramming of nasal basal cells by the chronic inflammatory environment. Finally, we will phenotype the submucosal nasal B-cells for IgA production and compare those of CRS patients with healthy subjects.

Date:1 Oct 2020 →  Today
Keywords:IgA, Immunology, Microbiome
Disciplines:Allergology, Inflammation, Innate immunity, Microbiome
Project type:PhD project