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Andreas, N.* ; Potthast, M. ; Geiselhöringer, A.-L. ; Garg, G.* ; de Jong, R.J. ; Riewaldt, J.* ; Russkamp, D. ; Riemann, M.* ; Girard, J.-P.* ; Blank, S. ; Kretschmer, K.* ; Schmidt-Weber, C.B. ; Korn, T.* ; Weih, F.* ; Ohnmacht, C.

RelB deficiency in dendritic cells protects from autoimmune inflammation due to spontaneous accumulation of tissue T regulatory cells.

J. Immunol. 203, 2602-2613 (2019)
Verlagsversion Postprint DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Foxp(3+) regulatory T cells are well-known immune suppressor cells in various settings. In this study, we provide evidence that knockout of the relB gene in dendritic cells (DCs) of C57BL/6 mice results in a spontaneous and systemic accumulation of Foxp(3+) T regulatory T cells (Tregs) partially at the expense of microbiota-reactive Tregs. Deletion of nfkb2 does not fully recapitulate this phenotype, indicating that alternative NF-kappa B activation via the RelB/p52 complex is not solely responsible for Treg accumulation. Deletion of Re1B in DCs further results in an impaired oral tolerance induction and a marked type 2 immune bias among accumulated Foxp(3+) Tregs reminiscent of a tissue Treg signature. Tissue Tregs were fully functional, expanded independently of IL-33, and led to an almost complete Treg-dependent protection from experimental autoimmune encephalomyelitis. Thus, we provide clear evidence that RelB-dependent pathways regulate the capacity of DCs to quantitatively and qualitatively impact on Treg biology and constitute an attractive target for treatment of autoimmune diseases but may come at risk for reduced immune tolerance in the intestinal tract.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Multiorgan Inflammation; Immunological-tolerance; Mice Lacking; Reg-cells; Homeostasis; Il-33; Maintenance; Disruption; Expression; Immunity
ISSN (print) / ISBN 0022-1767
e-ISSN 1550-6606
Zeitschrift Journal of Immunology
Quellenangaben Band: 203, Heft: 7, Seiten: 2602-2613 Artikelnummer: , Supplement: ,
Verlag American Association of Immunologists
Verlagsort 9650 Rockville Pike, Bethesda, Md 20814 Usa
Begutachtungsstatus Peer reviewed