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Martinez, G.J.* ; Pereira, R.M.* ; Äijö, T.* ; Kim, E.Y.* ; Marangoni, F.* ; Pipkin, M.E.* ; Togher, S.* ; Heissmeyer, V. ; Zhang, Y.C.* ; Crotty, S.* ; Lamperti, E.D.* ; Ansel, K.M.* ; Mempel, T.R.* ; Lähdesmäki, H.* ; Hogan, P.G.* ; Rao, A.*

The transcription factor NFAT promotes exhaustion of activated CD8+ T Cells.

Immunity 42, 265–278 (2015)
Verlagsversion DOI PMC
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
During persistent antigen stimulation, CD8(+) T cells show a gradual decrease in effector function, referred to as exhaustion, which impairs responses in the setting of tumors and infections. Here we demonstrate that the transcription factor NFAT controls the program of T cell exhaustion. When expressed in cells, an engineered form of NFAT1 unable to interact with AP-1 transcription factors diminished T cell receptor (TCR) signaling, increased the expression of inhibitory cell surface receptors, and interfered with the ability of CD8(+) T cells to protect against Listeria infection and attenuate tumor growth in vivo. We defined the genomic regions occupied by endogenous and engineered NFAT1 in primary CD8(+) T cells and showed that genes directly induced by the engineered NFAT1 overlapped with genes expressed in exhausted CD8(+) T cells in vivo. Our data show that NFAT promotes T cell anergy and exhaustion by binding at sites that do not require cooperation with AP-1.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chronic Viral-infection; Regulates Pd-1 Expression; Molecular-mechanisms; Tolerance; Tim-3; Dna; Calcineurin; Proteins; Calcium; Memory
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 1074-7613
e-ISSN 1097-4180
Zeitschrift Immunity
Quellenangaben Band: 42, Heft: 2, Seiten: 265–278 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501792-001
PubMed ID 25680272
DOI 10.1016/j.immuni.2015.01.006
WOS ID WOS:000349916400011
Scopus ID 84923026945
Erfassungsdatum 2015-05-06
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