Abstract Details

Title Astrocyte and CD4+ T cell interactions influence functional gene expression patterns under resting and pro-inflammatory conditions

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 136

Objective To test how contact between astrocytes and helper T cells drives changes in functional gene expression of both cell types under resting and pro-inflammatory conditions.

Background In multiple sclerosis (MS) lesions, immune cells must cross the two walls of the blood brain barrier to attack the central nervous system. Between the first wall (the vascular endothelium) and the second (a layer of astrocyte endfoot processes) is the perivascular space (PVS), a compartment where immune cells accumulate within both active and chronic MS lesions. Here, immune cells contact the astrocyte endfeet before entering the CNS. The functional consequences of this interaction have not been studied in detail.

Design/Methods We treated human astrocytes with saline or 20ng/ml of interleukin-1β (IL-1β) in vitro for 24 hours, then left them in isolation or paired them with CD3/CD28 activated human CD4+ T cells for 24 hours. Astrocytes cultured in isolation or under paired conditions after both saline and IL-1β treated conditions were harvested for RNA sequencing along with CD3/CD28 activated human CD4+ T cells cultured in isolation or under paired conditions. RNA sequencing of samples was performed using an ultra-low RNA input cDNA library preparation with polyA selection and paired end 150 base pair RNA sequencing with 20-30 million reads per sample.

Results Gene expression and functional pathway analyses comparing astrocytes in isolation and paired with CD4+ T cells, under resting and IL-1β treated conditions were performed, as were analyses comparing CD4+ T cells in isolation and after pairing with resting and activated astrocytes.

Conclusions

Resting and reactive astrocytes interact with helper T cells to induce specific functional gene expression patterns. Future next steps will involve exploring acute vs. chronic inflammatory changes, validating candidate pathways in vivo and testing translational strategies manipulating these pathways in the animal model of multiple sclerosis.

Authors/Disclosures
Sam H. Horng, MD, PhD PRESENTER	The institution of Dr. Horng has received research support from National Institutes of Health . The institution of Dr. Horng has received research support from Jayne and Harvey Beker Foundation .
	No disclosure on file
	No disclosure on file
Mario Amatruda (Icahn School of Medicine at Mount Sinai)	No disclosure on file

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