title: Postbiotic Modulation of Retinoic Acid Imprinted Mucosal-like Dendritic Cells by Probiotic Lactobacillus reuteri 17938 In Vitro.
abstract: Lactobacilli are widely used as probiotics with beneficial effects on infection-associated diarrhea, but also used in clinical trials of e.g., necrotizing enterocolitis and inflammatory bowel diseases. The possibility of using probiotic metabolic products, so-called postbiotics, is desirable as it could prevent possible side effects of live bacteria in individuals with a disturbed gut epithelial barrier. Here, we studied how Lactobacillus reuteri DSM 17938 cell-free supernatant (L. reuteri-CFS) influenced retinoic acid (RA)-driven mucosal-like dendritic cells (DC) and their subsequent effect on T regulatory cells (Treg) in vitro. RA clearly imprinted a mucosal-like DC phenotype with higher IL10 production, increased CD103 and CD1d expression, and a downregulated mRNA expression of several inflammatory-associated genes (NFκB1, RELB, and TNF). Treatment with L. reuteri-CFS further influenced the tolerogenic phenotype of RA-DC by downregulating most genes involved in antigen uptake, antigen presentation, and signal transduction as well as several chemokine receptors, while upregulating IL10 production. L. reuteri-CFS also augmented CCR7 expression on RA-DC. In cocultures, RA-DC increased IL10 and FOXP3 expression in Treg, but pre-treatment with L. reuteri-CFS did not further influence the Treg phenotype. In conclusion, L. reuteri-CFS modulates the phenotype and function of mucosal-like DC, implicating its potential application as postbiotic.
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , Stockholm , Sweden.
authors.forename: Yeneneh
authors.initials: Y
authors.lastname: Haileselassie
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , Stockholm , Sweden.
authors.forename: Marit
authors.initials: M
authors.lastname: Navis
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , Stockholm , Sweden.
authors.forename: Nam
authors.initials: N
authors.lastname: Vu
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , Stockholm , Sweden.
authors.forename: Khaleda Rahman
authors.initials: KR
authors.lastname: Qazi
authors.affiliation: Department of Medicine, Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Bence
authors.initials: B
authors.lastname: Rethi
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , Stockholm , Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Sverremark-Ekström
keywords: Lactobacillus reuteri; dendritic cells; postbiotics; probiotics; retinoic acid