Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases

Autor: Eva Michaud, Louis Waeckel, Rémi Gayet, Roman Goguyer‐Deschaumes, Blandine Chanut, Fabienne Jospin, Katell Bathany, Magali Monnoye, Coraline Genet, Amelie Prier, Caroline Tokarski, Philippe Gérard, Xavier Roblin, Nicolas Rochereau, Stéphane Paul
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 14, Iss 8, Pp 1-21 (2022)
Druh dokumentu: article
ISSN: 20211538
1757-4676
1757-4684
DOI: 10.15252/emmm.202115386
Popis: Abstract Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse‐transcytosis, the apical‐to‐basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan–glycan interaction. Here, we asked whether IgA1 and IgA2‐microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLC‐purified IgA, we show that reverse‐transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA‐bound microbiota in CD and UC showed distinct IgA1‐ and IgA2‐associated microbiota; the IgA1+ fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti‐glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis.
Databáze: Directory of Open Access Journals
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