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Ogawa, C.* ; Bankoti, R.* ; Nguyen, T.* ; Hassanzadeh-Kiabi, N.* ; Nadeau, S.* ; Porritt, R.A.* ; Couse, M.* ; Fan, X.* ; Dhall, D.* ; Eberl, G.* ; Ohnmacht, C. ; Martins, G.A.*

Blimp-1 functions as a molecular switch to prevent inflammatory activity in Foxp3+ ROR gamma t+ regulatory T cells.

Cell Rep. 25, 19-28.e5 (2018)
Verlagsversion Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Foxp3(+) regulatory T cells (Treg) are essential modulators of immune responses, but the molecular mechanisms underlying their function are not fully understood. Here we show that the transcription factor Blimp-1 is a crucial regulator of the Foxp3(+)ROR gamma t(+) Treg subset. The intrinsic expression of Blimp-1 in these cells is required to prevent production of Th17-associated cytokines. Direct binding of Blimp-1 to the II17 locus in Treg is associated with inhibitory histone modifications but unaltered binding of ROR gamma t. In the absence of Blimp-1, the II17 locus is activated, with increased occupancy of the co-activator p300 and abundant binding of the transcriptional regulator IRF4, which is required, along with ROR gamma t, for IL-17 expression in the absence of Blimp-1. We also show that despite their sustained expression of Foxp3, Blimp-1(-/-) ROR gamma t(+)IL-17-producing Treg lose suppressor function and can promote intestinal inflammation, indicating that repression of Th17-associated cytokines by Blimp-1 is a crucial requirement for ROR gamma t(+) Treg function.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Blimp-1 ; Foxp3 ; Il-17 ; Irf4 ; Prdm1 ; Rorγt ; Treg ; Intestinal ; Transcription; Transcriptional Repressor Blimp-1; Ror-gamma-t; Foxp3; Differentiation; Homeostasis; Specification; Expression; Tolerance; Induce; Irf4
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 25, Heft: 1, Seiten: 19-28.e5 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Allergy Research (IAF)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Allergy
PSP-Element(e) G-505400-001
DOI 10.1016/j.celrep.2018.09.016
WOS ID WOS:000446102400003
Scopus ID 85053658086
PubMed ID 30282028
Erfassungsdatum 2018-10-02
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