2024-03-29T01:26:22Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/65142022-11-08T11:15:16Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2145com_20.500.12105_2144col_20.500.12105_16980col_20.500.12105_16938col_20.500.12105_2146
00925njm 22002777a 4500
dc
Toribio-Fernandez, Raquel
author
Zorita, Virginia
author
Rocha-Perugini, Vera
author
Iborra, Salvador
author
Martinez del Hoyo, Gloria
author
Chevre, Raphael
author
Dorado, Beatriz
author
Sancho, David
author
Sanchez-Madrid, Francisco
author
Andres, Vicente
author
Gonzalez-Granado, Jose Maria
author
2018
Differentiation of naive CD4(+) T-cells into functionally distinct T helper (Th) subsets is critical to immunity against pathogen infection. Little is known about the role of signals emanating from the nuclear envelope for T-cell differentiation. The nuclear envelope protein lamin A/C is induced in naive CD4(+) T-cells upon antigen recognition and acts as a link between the nucleus and the plasma membrane during T-cell activation. Here we demonstrate that the absence of lamin A/C in naive T-cell reduces Th1 differentiation without affecting Th2 differentiation in vitro and in vivo. Moreover, Rag1(-/-) mice reconstituted with Lmna(-/-)CD4(+)CD25(-) T-cells and infected with vaccinia virus show weaker Th1 responses and viral removal than mice reconstituted with wild-type T-cells. Th1 responses and pathogen clearance upon Leishmania major infection were similarly diminished in mice lacking lamin A/C in the complete immune system or selectively in T-cells. Lamin A/C mediates Th1 polarization by a mechanism involving T-bet and IFN gamma production. Our results reveal a novel role for lamin A/C as key regulator of Th1 differentiation in response to viral and intracellular parasite infections.
Cell Death Dis. 2018; 9(1):9
2041-4889
http://hdl.handle.net/20.500.12105/6514
29311549
10.1038/s41419-017-0007-6
Cell Death and Disease
CD8(+) T-CELLS
CUTANEOUS LEISHMANIASIS
DENDRITIC CELLS
TRANSCRIPTION FACTOR
LINEAGE COMMITMENT
NUCLEAR-ENVELOPE
C57BL/6 MICE
C-FOS
IMMUNITY
EFFECTOR
Lamin A/C augments Th1 differentiation and response against vaccinia virus and Leishmania major