Histone deacetylase 6 at crossroads of infection and innnate immunity

• Autores: Olga Moreno Gonzalo
• Directores de la Tesis: Francisco Sánchez Madrid (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2018
• Idioma: español
• Número de páginas: 282
• Tribunal Calificador de la Tesis: Manuel Fresno Escudero (presid.), Juan Manuel Serrador Peiró (secret.), José Ramón Regueiro González-Barros (voc.), Ángel Luis Corbi Lopez (voc.), Carlos Martín Montañés (voc.)
• Programa de doctorado: Programa de Doctorado en Biociencias Moleculares por la Universidad Autónoma de Madrid
• Materias:
  • Ciencias de la vida
    • Inmunología
  • Ciencias médicas
    • Ciencias clínicas
      • Microbiología clínica
• Enlaces
  • Tesis en acceso abierto en: Biblos-e Archivo
• Resumen

  • 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 in CD8+ 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 (IFNγ) production. Our results establish HDAC6 as an effector of the immune cytotoxic response that acts by affecting the dynamics, transport and secretion of lytic granules by CTLs