Download Role of the immune cells recognizing MHC-I like

Studying the role of non-conventional immune cells in central nervous
system pathologies
CEDILE Oriane
NICN, CNRS UMR 6184 - IFR Jean Roche, Faculté de médecine Nord
51 Bd Pierre Dramard 13916 Marseille cedex 20
Tél: 04.91.69.87.75
Fax: 04.91.25.89.70
Courriel: [email protected]
Directeur de thèse: Docteur José BOUCRAUT
CNS pathologies, including neurodegenerative processes, are characterized by the presence of
immune cell infiltration, which is however not well characterized. We address the question of
the recruitment and the role of non-conventional immune cell populations, NK, NKT and T
gamma-delta lymphocytes infiltrating CNS in mouse experimental models such as olfactory
axotomy and EAE. It was previously showed that NK and NKT cells display neuroprotective
effects during EAE. The actions of these immune cells depend on the expression of MHC-Ia,
Ib or MHC-like molecules.
We first performed microdissections of adult CNS in physiological and pathological
conditions for a transcriptional analysis of the expression of numerous members of MHC
class I molecules and markers of immune cell populations. We will essentially describe the
results about the expression of CD1d and Rae-1. CD1d is constitutively expressed and the
higher expression is observed in the subventricular zone (SVZ). A weak expression of Rae-1
is detected solely in the SVZ of normal brain and its expression is strongly induced in the
olfactory bulbs after olfactory axotomy and in the spinal cord after EAE. In parallel, we
characterized the recruitment in pathological conditions of immune cells expressing the Rae-1
receptor NKG2D including NK cells. Our objective is now identifying the nature of the cells
expressing Rae-1. We observed that Rae-1 was expressed in culture by neural progenitors
obtained from the SVZ also expressing CD1d but not the MHC-Ia or Ib molecules nor the
β2m. We will thus analyze the action of NK and NKT cells on proliferation, survival and
differentiation of neural stem cells.
In order to elucidate the function of NKG2D expressing cells, we established a strategy of
inhibition of Rae-1 expression with lentivirus coding for RNAi and EGFP. We validated this
approach in vitro on neural stem cells and unexpectedly our results suggested that Rae-1 has
non-immune functions in neural cells. We will then inject the lentivirus in vivo before and
after induction of pathology.