Abstract Details

Title Distinct Immune Cell Subsets Influence Astrocytes To Express Factors Relevant for Myelin Repair

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 169

Objective

Background BACKGROUND: In multiple sclerosis (MS), complex interactions between lymphocytes, myeloid cells, and resident CNS cells are on one hand thought to promote injury, yet may also promote neuroprotection and myelin repair. In particular, factors released by pro-inflammatory (Th1/Th17/M1-polarized) immune cells promote CNS damage, while factors released by anti-inflammatory (Th2/M2-polarized) immune cells promote repair. Astrocytes, which are highly abundant in inflammatory MS lesions, can directly interact with and respond to secreted immune cell factors and serve as antigen presenting cells. Given this, we examined how pro- and anti-inflammatory immune cells could influence astrocyte expression of OPC growth factors relevant for myelin repair.

Design/Methods DESIGN/METHODS: PBMCs were isolated from healthy human volunteers, and polarized to either Th1/Th17/Th2 or M1/M2 phenotypes, respectively. Astrocytes derived from human fetal brain tissue were then incubated with supernatants of these immune cell subsets for 48 hours. Following incubation, qPCR was used to measure levels of PDGF-A, FGF-2, IGF-1, TIMP-1, IL-6, CNTF, and LIF expressed by astrocytes.

Results RESULTS: Pro-inflammatory M1-polarized supernatants significantly increased astrocyte expression of PDGF-A (p=0.007), TIMP-1 (p=0.0019), and LIF (p=0.034) as compared to either untreated or M2-polarized supernatants. Both pro- and anti-inflammatory conditions reduced astrocyte CNTF expression as compared to untreated controls. Relative to Th2- and M2-polarized supernatants, treatment with pro-inflammatory Th17- and M1- polarized supernatants decreased astrocyte CNTF expression 3-fold. Pro-inflammatory supernatants reduced astrocyte IGF-1 expression 4-fold as compared to both control and anti-inflammatory supernatants.

Conclusions CONCLUSIONS: Taken together, our results suggest that astrocytes can express OPC growth factors in response to both pro- and anti-inflammatory conditions. This differential pattern of growth factor expression may play an important role in both reducing damage and promoting myelin repair in the CNS.

Authors/Disclosures
Nebras Warsi PRESENTER	No disclosure on file
Craig S. Moore, PhD (Memorial University of Newfoundland)	Dr. Moore has nothing to disclose.
Jack P. Antel, MD, FAAN (Montreal Neurologic Hospital)	Dr. Antel has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for sanofi, roche, biogen, wave,nervgen. The institution of Dr. Antel has received research support from Novartis canada bristol myers squib. Dr. Antel has a non-compensated relationship as a past president with ACTRIMS that is relevant to AAN interests or activities.
Amit Bar-Or, MD, FRCPC (University of Pennsylvania)	Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.
Norman Putzki, MD (Novartis Pharma AG)	No disclosure on file

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