Abstract Details

Title Partial Deprivation of the DC-Poietin FLT3L Protects Animals from Experimental Autoimmune Encephalomyelitis

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 172

Objective

Background BACKGROUND: FLT3L, ligand for the fms-like tyrosine kinase 3 recruits plasmacytoid DC to the brain. FLT3 is required for DC development in peripheral lymphoid tissues. DCs participate to multiple sclerosis (MS) pathogenesis. Increased expression of the FLT3 has been detected in brains from MS patients on infiltrating DCs and activated microglia cells. In mice, CD11c+ DC are sufficient to present antigen in vivo to primed myelin-reactive T cells and to mediate CNS inflammation.

Design/Methods DESIGN/METHODS: We used heterozygous mice for flt3l, displaying a functional blood cell homeostasis and a presumably defect of DC maturation. We assessed the level of flt3l mRNA on spleen cells and evaluated the disease course in C57BL/6-FLT3+/- mice compared with wild type (WT). Immunization was performed with MOG35-55 peptide. Inflammatory cells were isolated from spleens and spinal cords, and analyzed by flow cytometry. DCs from WT and FLT3L+/- mice were studied for their activation status and capacity to present MOG to antigen specific CD4+ T cells.

Results RESULTS: FLT3L is significantly reduced in the spleens of FLT3L+/- mice. The course of EAE was significantly reduced in FLT3L+/- mice vs. WT. The protection observed in FLT3L+/- EAE mice is associated with a dramatic decrease of DC infiltration in the CNS. By contrast, CNS macrophages and infiltrating lymphocytes are similar in both groups. We observed a reduced capacity of splenic FLT3L+/- DCs to present antigen to MOG-specific T cells.

Conclusions CONCLUSIONS: Our results indicate that FLT3L plays a critical role in the development of CNS autoimmunity through the maturation of DCs and further define the potential role of deregulated activation of DCs in the pathogenesis of EAE. Hence, FLT3 signaling could be considered as a potential target for therapeutic approaches in CNS autoimmune diseases such as MS.

Authors/Disclosures
Marie-Laure Santiago-Raber, PhD PRESENTER	No disclosure on file
Patrice LaLive, MD	Dr. LaLive has nothing to disclose.
	No disclosure on file
	No disclosure on file
Diego Centonze	Diego Centonze has nothing to disclose.

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