PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Essig, K.* ; Hu, D.* ; Guimaraes, J.C.* ; Alterauge, D.* ; Edelmann, S.L. ; Raj, T.* ; Kranich, J.* ; Behrens, G.* ; Heiseke, A.F.* ; Floess, S.* ; Klein, J.* ; Maiser, A.* ; Marschall, S. ; Hrabě de Angelis, M. ; Leonhardt, H.* ; Calkhoven, C.F.* ; Nößner, E. ; Brocker, T.* ; Huehn, J.* ; Krug, A.B.* ; Zavolan, M.* ; Baumjohann, D.* ; Heissmeyer, V.

Roquin suppresses the PI3K-mTOR signaling pathway to inhibit T helper cell differentiation and conversion of treg to Tfr cells.

Immunity 47, 1067-1082.e12 (2017)
Publ. Version/Full Text DOI PMC
Closed
Open Access Green as soon as Postprint is submitted to ZB.
Roquin proteins preclude spontaneous T cell activation and aberrant differentiation of T follicular helper (Tfh) or T helper 17 (Th17) cells. Here we showed that deletion of Roquin-encoding alleles specifically in regulatory T (Treg) cells also caused the activation of conventional T cells. Roquin-deficient Treg cells downregulated CD25, acquired a follicular Treg (Tfr) cell phenotype, and suppressed germinal center reactions but could not protect from colitis. Roquin inhibited the PI3K-mTOR signaling pathway by upregulation of Pten through interfering with miR-17 92 binding to an overlapping cis-element in the Pten 3' UTR, and downregulated the Foxo1-specific E3 ubiquitin ligase Itch. Loss of Roquin enhan ced Akt-mTOR signaling and protein synthesis, whereas inhibition of PI3K or mTOR in Roquin-deficient T cells corrected enhanced Tfh and Th17 or reduced iTreg cell differentiation. Thereby, Roquin-mediated control of PI3K-mTOR signaling prevents autoimmunity by restraining activation and differentiation of conventional T cells and specialization of Treg cells. Essig et al. show that spontaneous activation and aberrant differentiation of Roquin-deficient T cells involves cell-intrinsic causes in not only conventional T cells but also impaired Treg cell function. In both cell types, Roquin inhibits the PI3K-mTOR signaling pathway at several levels, thereby controlling protein biosynthesis and limiting differentiation toward Th17 and Tfh cells as well as preventing the conversion and functional specialization of Treg into Tfr cells.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
22.845
4.611
74
89
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Akt Mtor ; Cd25 ; Foxo1 ; Itch ; Pten ; Rna-binding Proteins ; Roquin ; T Cell Differentiation ; Tfh ; Tfr; Costimulator Messenger-rna; Germinal Center Reaction; Th17 Differentiation; Effector Lineage; Ror-gamma; Expression; Mtor; Autoimmunity; Inflammation; Receptor
Language english
Publication Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 1074-7613
e-ISSN 1097-4180
Journal Immunity
Quellenangaben Volume: 47, Issue: 6, Pages: 1067-1082.e12 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Immune Regulation (AMIR)
Institute of Experimental Genetics (IEG)
Institute of Virology (VIRO)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30201 - Metabolic Health
Research field(s) Immune Response and Infection
Genetics and Epidemiology
PSP Element(s) G-501712-001
G-500600-001
G-502710-001
DOI 10.1016/j.immuni.2017.11.008
WOS ID WOS:000418486500012
Scopus ID 85037721497
PubMed ID 29246441
Erfassungsdatum 2017-12-28
[➜Report correction]