Lamin A/C augments Th1 differentiation and response against vaccinia virus and Leishmania major
| Autor: | David Sancho, Raquel Toribio-Fernández, Vicente Andrés, Vera Rocha-Perugini, Virginia Zorita, Beatraiz Dorado, Salvador Iborra, Gloria Martínez del Hoyo, Francisco Sánchez-Madrid, Raphael Chevre, José-María González-Granado |
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| Přispěvatelé: | UAM. Departamento de Medicina, Instituto de Investigación del Hospital de La Princesa (IP), Instituto de Salud Carlos III, Fundación Ramón Areces, Fondation ACTERIA (Acting on European Research in Immunology and Allergology), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Ministerio de Economía, Industria y Competitividad (España), Fundación ProCNIC, Research Institute Hospital 12 de Octubre |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Cancer Research CUTANEOUS LEISHMANIASIS Cellular differentiation Lymphocyte Activation LMNA C57BL/6 MICE Mice Differentation T-cell Vaccinia Cytotoxic T cell Leishmania major TRANSCRIPTION FACTOR NUCLEAR-ENVELOPE Mice Inbred BALB C lcsh:Cytology Cell Differentiation Lamin Type A 3. Good health Cell biology Virus medicine.anatomical_structure Disease Susceptibility C-FOS Medicina T cell Immunology EFFECTOR Leishmaniasis Cutaneous Vaccinia virus CD8(+) T-CELLS IMMUNITY Biology DENDRITIC CELLS Article 03 medical and health sciences Cellular and Molecular Neuroscience Interferon-gamma medicine Animals lcsh:QH573-671 Interleukin 4 Lamin A/C LINEAGE COMMITMENT Cell Biology Th1 Cells biology.organism_classification 030104 developmental biology Immune System Interleukin-4 T-Box Domain Proteins Lamin |
| Zdroj: | Cell Death and Disease, Vol 9, Iss 1, Pp 1-15 (2018) Biblos-e Archivo. Repositorio Institucional de la UAM instname Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Cell Death & Disease Repisalud Instituto de Salud Carlos III (ISCIII) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-017-0007-6 |
| Popis: | 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. The authors thank J. Mateos, I. Fernandez-Lopez, and M.J. Andres-Manzano for technical assistance and S. Bartlett for English editing. This study was supported by grants to J.-M.G.-G. from Instituto de Salud Carlos III (ISCIII) (PI14/00526, PI17/01395, CP11/00145, CPII16/00022), the Miguel Servet Program, and Fundacion Ramon Areces; to V.A. (RD12/0042/0028 SAF2013-46663-R, SAF2016-79490-R); to F.S.-M. (SAF2014-55579-R, INDISNET-S2011/BMD-2332, ERC-2011-AdG 294340-GENTRIS, and PIE13/00041); and to D.S. (SAF-2013-42920R, SAF2016-79040-R, and Fondation ACTERIA) with co-funding from the Fondo Europeo de Desarrollo Regional (FEDER). The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MEIC) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). S.I. is funded by grant SAF2015-74561-JIN, R.T.-F. by the Fundacion Ramon Areces, V.Z. by ISCIII, and J.-M.G.-G. by the ISCIII Miguel Servet Program and the Instituto de Investigacion Sanitaria Hospital 12 de Octubre (imas12). Sí |
| Databáze: | OpenAIRE |
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