Role of dendritic cells in ischemia-induced neuroinflammation

Description

This project aims to elucidate the function of dendritic cells in stroke by deleting or expanding this cell population. Dendritic cells will be depleted using CD11c.DTR mice, in which dendritic cells express the diphtheria toxin (DT) receptor under control of CD11c, a marker of mouse dendritic cells. By injecting CD11c.DTR mice with DT CD11c+ cells, such as dendritic cells, will be selectively ablated. On the other hand, partner 2 will induce dendritic cell expansion. Specific expansion of CD11c+B220+ plasmacytoid dendritic cells has been reported in the liver. However, how these dendritic cell subpopulations behave in the brain after stroke is unknown. The effect of dendritic cell modulation on the time course of the inflammatory cytokine profile will be examined in the brain by RT-PCR and by using cytokine arrays in cooperation with partner 14. Flow cytometry will be employed to detect immune cells. In the same animals, partner 2 will monitor the progression of brain injury by using non-invasive MRI, conducting longitudinal studies to follow the progression of the brain lesion, and the neurological deficits will be monitored with behavioural tests. Blood samples of mice will be provided to partner 13 for the detection of autoantibodies.

Publications

  • Chamorro A, Urra X, Planas AM (2007) Infection after acute ischemic stroke: a manifestation of brain-induced immunodepression. Stroke 38:1097-1103
  • Rojas S, Martín A, Arranz MJ, Pareto D, Purroy J, Verdaguer E, Llop J, Gómez V, Gispert JD, Millán O, Chamorro A, Planas AM (2007) Imaging brain inflammation with [11C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats. J Cereb Blood Flow Metab 27:1975-86

Tasks and methodology

  • Deleting dendritic cells with the help of CD11c.DTR mice
  • Inducing dendritic cell expansion
  • Determination of inflammatory cytokines using quantitative RT-PCR and cytokine arrays
  • Flow cytometry
  • MRI, behavioural tests

Planned secondment

University Medical Center Hamburg Eppendorf, Investigation of dendritic cell activation by innate immunity; Euroimmun AG, Detection of autoantibodies, 10 months