Abstract Details

Title Identification of a Unique Microglial Signature in Mice and Humans

Topic MS and Related Diseases

Presentation(s) S50 - (-)

Poster/Presentation
Number 001

Objective

Background Microglia are resident myeloid-lineage cells in the CNS that function in the maintenance of normal tissue. To date there are no unique markers for microglia cells. The distinction between resident microglia and recruited mononuclear phagocytes is crucial, because it provides an approach to understand the biology of microglia and their relevance to disease.

Design/Methods We used three approaches to identify unique biological features of microglial cells: 1) generation of monoclonal antibodies against surface molecules on CNS derived adult microglia vs. peripheral monocytes; 2) gene and microRNA array analysis of these two populations and other immune cells; and 3) quantitative proteomic analysis between CNS derived adult microglia vs. peripheral Ly6C monocytes.

Results We have identified a microRNA/gene signature that is uniquely expressed in resident adult microglia in mice and humans. This molecular microglial signature was not observed in classically studied microglial cell lines or embryonic preparations of microglia, nor in peripheral immune cells or recruited mononuclear cells in animal models of MS, AD or ALS. Moreover, most of the identified unique microglial genes were downregulated during acute or chronic phases in EAE mice or during disease progression in ALS and AD. In freshly isolated post-mortem MS tissue, we identified activated microglia in association with plaques but not in unaffected brain regions. As part of this unique microglial signature, we identified unique surface markers related to TAM receptors. Targeting these receptors modulated microglia from an M1 to M2 phenotype both in vitro and in vivo.

Conclusions Our findings redefine resident microglia as highly active in homeostasis and regulation of immune responses. They provide a new definition of resident microglia and utilize unique tools and methods which have not been available previously to address the biology of microglia in normal brain function and in neurologic disease.

Authors/Disclosures
Oleg Butovsky, PhD (Brigham and Women's Hospital/Harvard Medical) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	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.
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..

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