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oai:repisalud.isciii.es:20.500.12105/65142024-11-28T16:04:54Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19605col_20.500.12105_16938col_20.500.12105_16980

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 10.1038/s41419-017-0007-6 2041-4889 Cell Death and Disease 29311549 http://hdl.handle.net/20.500.12105/6514 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