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Abstract Details

Regulation of Human CNS Myeloid Cell Inflammatory Responses by mir-155
MS and Related Diseases
S50 - (-)
005
Innate immune responses in the CNS reflect contributions from both peripheral-derived macrophages and resident microglia. Under basal and polarizing conditions, we have previously shown that human macrophages and microglia possess distinct phenotypic and functional properties. We hypothesize that expression of distinct miRNAs may provide insight into the molecular mechanisms responsible for these unique properties. Identifying differential expression patterns of miRNAs in myeloid cells of MS patients may provide valuable insight into their capacity to influence CNS injury and repair.
For in situ studies, laser-capture microdissection (LCM) was used to isolate perivascular and parenchymal CD68+ cells from formalin-fixed control and MS brain samples. CD14+ monocytes were isolated from PBMCs of MS patients and controls. For in vitro studies, microglia were isolated from fetal tissue and tissues from patients undergoing surgery for intractable epilepsy; macrophages were generated from CD14+ monocytes isolated from PBMCs of healthy volunteers. Cell polarization (M1/M2) was performed using previously validated protocols. MiRNA expression was determined by TaqMan qPCR miRNA expression assays.
In the MS brain, mir-155 expression was significantly increased in parenchymal CD68+ cells. In situ and in vitro studies demonstrated that basal expression of mir-155 was lower in microglia/parenchymal cells compared to macrophages. Under M1 conditions, mir-155 expression was significantly increased in both macrophages and microglia. Analysis of CD14+ monocytes from untreated MS patients showed that mir-155 expression was significantly elevated compared to controls. Transfection of mir-155 mimics increased pro-inflammatory cytokine secretion and CD80 expression in both cell types; mir-155 inhibitors decreased pro-inflammatory cytokine expression.
Our results demonstrate that mir-155 regulates pro-inflammatory responses in both blood-derived (macrophages) and CNS-resident (microglia) myeloid cells, both of which participate in active lesions in MS.
Authors/Disclosures
Craig S. Moore, PhD (Memorial University of Newfoundland)
PRESENTER 		Dr. Moore has nothing to disclose.
Vijayaraghava T. Rao, PhD (argenx US Inc) No disclosure on file
No disclosure on file
No disclosure on file
Samuel Ludwin, MD (Kingston General Hospital) No disclosure on file
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.
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.
Krzysztof W. Selmaj (University of Warmia and Mazury) Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astra. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.