Toribio-Fernandez, RaquelZorita, VirginiaRocha-Perugini, VeraIborra, SalvadorMartinez del Hoyo, GloriaChevre, RaphaelDorado, BeatrizSancho, DavidSanchez-Madrid, FranciscoAndres, VicenteGonzalez-Granado, Jose Maria2018-10-252018-10-252018Cell Death Dis. 2018; 9(1):92041-4889http://hdl.handle.net/20.500.12105/6514Differentiation 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.engVoRhttp://creativecommons.org/licenses/by/4.0/CD8(+) T-CELLSCUTANEOUS LEISHMANIASISDENDRITIC CELLSTRANSCRIPTION FACTORLINEAGE COMMITMENTNUCLEAR-ENVELOPEC57BL/6 MICEC-FOSIMMUNITYEFFECTORAtribución 4.0 Internacional29311549910.1038/s41419-017-0007-6Cell Death and Diseaseopen access