Abstract Details

Title Dimethyl Fumarate (DF) Suppresses GMCSF-producing Th1 cells in EAE and human CD4 T cells.

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-071

Objective

Dimethyl Fumarate(DF) acts directly on CD4 T cells and suppresses GMCSF producing Th1 cells in EAE and human PBMCs.

Background DF is an oral therapy for multiple sclerosis. DF treatment decreases the relapse rate and development of new, active brain lesions in patients, which suggests immuno-regulatory mechanism in inflammation besides its neuroprotective effects. However,DF induces IL-10 producing type II DCs,its direct role of DF on T cells is still unknown.

Design/Methods We collected splenocytes from C57BL/6 wild-type (WT) mice, and purified CD4 cells by milteny biotech microbeads. Cells were cultured with Anti CD3/CD28 in the presence/absence of DF. IFNg, IL-17 and GMCSF were measured by ELISA. Cells were analyzed by flow-cytometry. WT mice were immunized with MOG35–55 for EAE induction and treated with oral DF or vehicle daily. For experiments on human PBMCs, venous blood were collected from nine normal individuals and PBMCs were collected by percol gradient method,cultured and treated with DF/vehicle with Anti CD3/CD28 Ab for 5 days.

Results DF treatment reduced GMCSF and IFNg but not IL-17 in the supernatant of CD4 cells. DF significantly reduced GMCSF+/ IFNg +/CD4 T cells. In In-vivo experiments, DF subsides clinical EAE. Splenocytes from treated mice produced a smaller amount of GMCSF (430 vs 100 pg) and IFNg (820 vs 250pg) compared to control in culture. In addition, the number of infiltrating GMCSF+/Th1 cells in the CNS of control mice was four times more than treated mice. Furthermore, Inhuman PBMCs culture, DF decreased IFNg (3000 vs 870 pg), measured by ELISA, in the supernatant, and FACS analysis demonstrated 56% reduction of GMCSF+/ Th1 cells in DF-treated cells.

Conclusions DF acts directly on CD4 T cells and suppresses GMCSF production in Th1 cells. Above findings expand our understanding about direct immuno-regulatory mechanism of DF in CD4 T cells leading to reduction of immuno-pathogenicity of these cells.

Authors/Disclosures
Farinaz Safavi, MD, PhD PRESENTER	The institution of Dr. Safavi has received research support from NMSS/ABF.
Zichen Li	No disclosure on file
	No disclosure on file
Mohamad Rostami, MD, PhD, FAAN (Thomas Jefferson University)	No disclosure on file

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