HDAC6 regulates the dynamics of lytic granules in cytotoxic T lymphocytes
Entity
UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)Publisher
The Company of Biologists Ltd.Date
2016-04-01Citation
10.1242/jcs.180885
Journal of Cell Science 129 (2016): 1305-1311
ISSN
0021-9533 (print); 1477-9137 (online)DOI
10.1242/jcs.180885Funded by
This work was supported by the Ministerio de Economı́a y competitividad (MINECO) [grant number SAF2014-55579-R]; Comunidad Autónoma de Madrid (CAM) [grant number INDISNET01592006]; Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) [grant numbers BIOMID-PIE13/041 and RD12/0042/0056]; European Research Council (ERC) [grant number ERC-2011-AdG 294340- GENTRIS]Project
Gobierno de España. SAF2014-55579-R; info:eu-repo/grantAgreement/EC/FP7/294340Editor's Version
http://dx.doi.org/10.1242/jcs.180885Subjects
Histone deacetylase 6; Kinesin 1; Lytic granule; MedicinaRights
© 2016.The Company of Biologists LtdAbstract
Journal of Cell Science.HDAC6 is a tubulin deacetylase involved in many cellular functions related to cytoskeleton dynamics, including cell migration and autophagy. In addition, HDAC6 affects antigen-dependent CD4+ T cell activation. In this study,we show that HDAC6 contributes to the cytotoxic function of CD8+ T cells. Immunization studies revealed defective cytotoxic activity in vivo in the absence of HDAC6. Adoptive transfer of wild-type or Hdac6-/- CD8+ T cells to Rag1-/- mice demonstrated specific impairment inCD8+ T cell responses against vaccinia infection. Mechanistically, HDAC6-deficient cytotoxic T lymphocytes (CTLs) showed defective in vitro cytolytic activity related to altered dynamics of lytic granules, inhibited kinesin-1-dynactin-mediated terminal transport of lytic granules to the immune synapse and deficient exocytosis, but not to target cell recognition, T cell receptor (TCR) activation or interferon (IFN)γ production. Our results establish HDAC6 as an effectorof theimmune cytotoxic response that acts byaffecting the dynamics, transport and secretion of lytic granules by CTLs.
Files in this item
Google Scholar:Núñez-Andrade, Norman
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Iborra, Salvador
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Trullo, Antonio
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Moreno-Gonzalo, Olga
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Calvo, Enrique
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Catalán. Elena
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Menasche, Gaël
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Sancho, David
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Vázquez, Jesús
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Yao, Tso-Pang
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Martı́n-Cófreces, Noa Beatriz
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Sánchez Madrid, Francisco
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