期刊
CELL DEATH & DISEASE
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41419-017-0007-6
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资金
- Instituto de Salud Carlos III (ISCIII) [PI14/00526, PI17/01395, CP11/00145, CPII16/00022]
- Miguel Servet Program
- Fundacion Ramon Areces [RD12/0042/0028 SAF2013-46663-R, SAF2016-79490-R, SAF2014-55579-R, INDISNET-S2011/BMD-2332, ERC-2011-AdG 294340-GENTRIS, PIE13/00041, SAF-2013-42920R, SAF2016-79040-R]
- Fundacion Ramon Areces (Fondation ACTERIA)
- Fondo Europeo de Desarrollo Regional (FEDER)
- Ministry of Economy, Industry and Competitiveness (MEIC)
- Pro CNIC Foundation
- Severo Ochoa Center of Excellence [SEV-2015-0505]
- Fundacion Ramon Areces
- ISCIII
- ISCIII Miguel Servet Program
- Instituto de Investigacion Sanitaria Hospital 12 de Octubre (imas12)
- [SAF2015-74561-JIN]
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.
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