Farnesol induces protection against CNS inflammatory demyelination and decreases spinal infiltration of CD4+ T-Cells

Abstract

Abstract Multiple Sclerosis (MS) is an autoimmune disease that causes T-cells to attack and degrade the myelin sheath of neurons in the spinal cord and brain. Farnesol is synthesized by plants and mammals and has anti-inflammatory along with neuroprotective activities. We used the MOG35–55 induced c57BL/6 murine EAE (experimental autoimmune encephalomyelitis) model due to model’s neurodegenerative and inflammatory properties. We predicted that farnesol would protect against EAE and increase autoimmunity markers. We collected spinal cords and spleens for flow cytometry analysis at the end of the study. This study found that farnesol significantly reduced spinal infiltration of CD4+ T cells, and increased infiltration of Tregs compared to untreated mice. Interestingly the proportion of CD25+Foxp3+ was increased compared to untreated mice, and statistically significant compared to vehicle treatment. We did not observe significant changes in CD4+, or CD25+Foxp3+ frequencies in the spleens. FOL treatment showed significant increase in CD11b+F4/80+ monocyte-derived macrophages (MDM) and F4/80int granulocytes/monocytes. FOL also showed significant weight retention and reduction of disease severity compared to untreated. These findings show that farnesol helps mediate the invasion of CD4+ T cells in the EAE model. Future studies should study how farnesol affects T-cell activation and differentiation, along with affects on macrophages and dendritic cells. This work was supported in part by the National Institutes of Health (grant R15NS107743)