NOD2 deficiency increases retrograde transport of secretory IgA complexes in Crohn's disease

• Published in: Nature communications Vol. 12; no. 1; p. 261
• Main Authors: Rochereau, Nicolas, Roblin, Xavier, Michaud, Eva, Gayet, Rémi, Chanut, Blandine, Jospin, Fabienne, Corthésy, Blaise, Paul, Stéphane
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 11.01.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adaptive immunity; Animals; Antigen-antibody complexes; Colitis - microbiology; Colitis - pathology; Commensals; Crohn Disease - metabolism; Crohn Disease - pathology; Crohn's disease; Digestive system; Digestive tract; Disease; Dysbacteriosis; Gut-associated lymphoid tissues; Humans; Immunoglobulin A; Immunoglobulin A, Secretory - metabolism; Inflammation; Inflammatory bowel diseases; Intestinal microflora; Intestine; Lectins, C-Type - metabolism; Lymphoid tissue; M cells; Mice; Mice, Knockout; Microbiota; Models, Biological; Mucosa; Mucosal immunity; Mutation; Mutation - genetics; NOD2 protein; Nod2 Signaling Adaptor Protein - deficiency; Nod2 Signaling Adaptor Protein - genetics; Nod2 Signaling Adaptor Protein - metabolism; Peyer's Patches - metabolism; Priming; Protein Transport; Retrograde transport; Salmonella - physiology; Sialic Acid Binding Immunoglobulin-like Lectins - metabolism; Transcytosis; Translocation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20348-0

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.