Abstract
Intestinal microfold cells are the primary pathway for translocation of secretory IgA (SIgA)-pathogen complexes to gut-associated lymphoid tissue. Uptake of SIgA/commensals complexes is important for priming adaptive immunity in the mucosa. This study aims to explore the effect of SIgA retrograde transport of immune complexes in Crohn’s disease (CD). Here we report a significant increase of SIgA transport in CD patients with NOD2-mutation compared to CD patients without NOD2 mutation and/or healthy individuals. NOD2 has an effect in the IgA transport through human and mouse M cells by downregulating Dectin-1 and Siglec-5 expression, two receptors involved in retrograde transport. These findings define a mechanism of NOD2-mediated regulation of mucosal responses to intestinal microbiota, which is involved in CD intestinal inflammation and dysbiosis.
Highlights
Intestinal microfold cells are the primary pathway for translocation of secretory IgA (SIgA)pathogen complexes to gut-associated lymphoid tissue
We initially examined whether the transport of SIgA was modified as a consequence of the disease, and second refined the analysis to samples collected from Crohn’s disease (CD) patients with or lacking NOD2 mutations
A second colocalization IgA2+/dendritic cell (DC)-SIGN+ (Fig. 1b) indicate that counted SIgA+ cells derived from the retrograde transport of SIgA through M cells followed by their DC uptake
Summary
Intestinal microfold cells are the primary pathway for translocation of secretory IgA (SIgA)pathogen complexes to gut-associated lymphoid tissue. NOD2 has an effect in the IgA transport through human and mouse M cells by downregulating Dectin-1 and Siglec-5 expression, two receptors involved in retrograde transport These findings define a mechanism of NOD2-mediated regulation of mucosal responses to intestinal microbiota, which is involved in CD intestinal inflammation and dysbiosis. SIgA exhibits the striking feature to adhere to the apical membrane of M cells, promoting the uptake and delivery of antigens (Ags) to dendritic cell (DC) located in Peyer’s patches (PP) Under pathological conditions such as infection invading IgA opsonized micro-organisms, these immune complexes amplifies the production of proinflammatory cytokines such as TNF, IL-1β, and IL-23 by human CD103 + DCs17. Our findings define a mechanism of NOD2-mediated regulation of innate immune responses to intestinal microbiota which is involved in the initiation and/or perpetuation of the mucosal inflammation observed in CD patients
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