Abstract Details

Title Impact of Oxysterols on the Gut-brain Axis During Experimental Autoimmune Encephalomyelitis

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (12:00 PM-1:00 PM)

Poster/Presentation
Number 9-008

Objective To assess the role of oxysterols in modulating the gut-brain axis during experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis.

Background

The role of cholesterol metabolism remains unclear during neuroinflammation. Cholesterol is hydroxylated into the oxysterol 25-hydroxycholestol by the enzyme cholesterol 25-hydroxylase (Ch25h). Ch25h-/- mice depict an attenuated EAE disease and increased levels of IgA in the intestinal mucosa compared to wild-type (WT) controls. Furthermore we observed altered gut-associated immune responses with accumulation of encephalitogenic Th17 cells in the gut during EAE together with a dysbiosis in WT mice.

Design/Methods Gut immune responses were assessed in Ch25h-/- and WT mice at steady state and at different time points during EAE disease. Chemokine, antimicrobial peptide and Ch25h expression profiles were assessed by real-time PCR, Immune cells isolated from intestinal lamina propria by flow cytometry. Histological evaluations were performed to assess intestinal morphological changes and inflammatory infiltrates of mouse intestine. Intestinal microbiome changes were evaluated by metataxonomics based on 16S rRNA marker gene.

Results We observed that Ch25h expression is increased in the small intestine during EAE development. Th17 cell infiltration in the small intestine during EAE is delayed in Ch25h-/- compared to wild-type mice. At structural level, we detected changes in villi length during EAE in WT but not in Ch25h-/- mice. No major differences in intestinal microbiome were observed between WT and Ch25h-/- mice during EAE.

Conclusions We here describe changes in intestinal immune responses during EAE in the absence of oxysterols independently of the gut microbiome. A better understanding of the interplay between lipid metabolism and intestinal immunity could contribute to understand the role of cholesterol metabolism during EAE and MS.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Caroline Pot Kreis, MD (Geneva University Hospital)	No disclosure on file

��ɫ��

��ɫ��