Abstract Details

Title Laquinimod Induces a Shift from Pro-inflammatory to Regulatory T Cells and Decreases Myeloid Dendritic Cells in Mice with Experimental Autoimmune Encephalomyelitis

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 149

Objective

Background BACKGROUND: LAQ is a new orally active, well tolerated drug which reduces relapse rate, brain atrophy and disability progression in patients with multiple sclerosis (MS). In animals LAQ suppresses acute EAE and inhibits relapses in chronic EAE. Central inflammation is reduced and the cytokine balance is shifted in favor of Th2/Th3 cytokines.

Design/Methods DESIGN/METHODS: C57BL/6 mice with MOG35-55-induced EAE were treated with 0 or 25 mg/kg LAQ administered daily from the day of immunisation until day 11. Single cell suspensions from lymph nodes and spleen were analysed by flow cytometry and ELISA.

Results RESULTS: Preventive treatment with LAQ significantly decreased the percentage of Th17 (p=0.0022) and Th1 T cells (p=0.026) among the CD4 T cell population. The absolute number of CD4 T cells producing IL-17 or IFN-? in response to PMA/ionomycin was also reduced after therapy. Spleen and lymph node cells of treated animals produced less of these cytokines in a recall assay with MOG35-55 compared to controls. Furthermore, the percentage of FoxP3 regulatory T cells increased with LAQ treatment (p=0.0022). Cells of the innate immune response were also affected by LAQ. FACS data revealed a significant reduction in CD11chigh dendritic cells (p=0.0013) in LAQ-treated animals. Within the dendritic cell population CD11b myeloid dendritic cells were significantly decreased (p=0.0001). In contrast, CD8? DEC205 dendritic cells, previously described as regulatory subtype, remained unaltered.

Conclusions CONCLUSIONS: In conclusion, preventive treatment with LAQ reduces dendritic cells and suppresses the pro-inflammatory autoimmune T cell response in mice with MOG35-55-induced EAE. These findings indicate that LAQ interferes with the priming and activation of innate and adaptive immune cells and may therefore play a role in future treatment of MS.

Authors/Disclosures
Christiane Wegner, MD (John Radcliffe Hospital) PRESENTER	No disclosure on file
	No disclosure on file
Stefan Nessler, MD (University Medical Center Goettingen)	No disclosure on file
Wolfgang Brueck, PhD (Zentrum Pathologie)	Dr. Brueck has nothing to disclose.
	No disclosure on file

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