| First Author | Toribio-Fernández R | Year | 2018 |
| Journal | Cell Death Dis | Volume | 9 |
| Issue | 1 | Pages | 9 |
| PubMed ID | 29311549 | Mgi Jnum | J:361189 |
| Mgi Id | MGI:6823104 | Doi | 10.1038/s41419-017-0007-6 |
| Citation | Toribio-Fernandez R, et al. (2018) Lamin A/C augments Th1 differentiation and response against vaccinia virus and Leishmania major. Cell Death Dis 9(1):9 |
| abstractText | 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 IFNgamma 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. |
