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Characterization of IL-1β Induced Signaling Across Immune Cell Subsets

Presenters Name: 
Mythili Vigneshwar
Co Presenters Name: 
Primary Research Mentor: 
Coleen McNamara
Secondary Research Mentor: 
Hema Kothari
9:30 - 10:15
Time of Presentation: 
2019 - 9:30am to 10:15am
Newcomb Hall Ballroom
Presentation Type: 
Presentations Academic Category: 
Grant Program Recipient: 
Harrison Undergraduate Research Grant

Background: When overactive, the interleukin-1 (IL-1) inflammatory pathway activates intracellular signaling in immune cells and causes cardiomyocyte apoptosis leading to larger infarct size, higher risk of atherosclerosis, and other CVD [1]. IL-1α and IL-1β are key cytokines of this pathway and bind to the IL-1 receptor (IL-1R1) to activate intracellular signaling [2]. Reducing inflammation through inhibition of IL-1β has recently emerged as a new therapy for reducing the risk of recurrent cardiovascular events in patients with prior history of CVD and elevated inflammation [3]. We proposed to characterized IL-1β induced signaling across all human immune cell subsets and to study the inhibitory effects of Anakinra, an IL-1R antagonist. Methods: Peripheral blood mononuclear cells were isolated from healthy donors and patients with CAD stimulated with IL-1β +/- Anakinra, stained with surface and intracellular markers, and run in mass cytometry. Data was analyzed in Flowjo and Cytobank. Results: Optimizing IL-1β dose for intracellular signaling showed optimal signals of phosphorylation of NF-kB, p38, and ERK 1 and 2 at 10 ng/mL after 15 minutes of IL-1β stimulation. IL-1β induced signaling was seen mainly in T cell subsets, and the signaling was inhibited by Anakinra. Finally, preliminary comparison of IL-1β induced phospho activation in patients with mild and severe CAD demonstrates increased activation in patients with high CAD. Conclusion: Our results implicate memory T cell subsets as crucial mediators of IL-1β induced inflammatory responses. Further studies are needed to gain insight into the functions of these T cell subsets in inflammation and heart disease. References: 1. Van Tassell BW, Toldo S, Mezzaroma E, Abbate A. Circulation. 2013;128(17);1910-23. 2. Garlanda C, Dinarello A, C, Mantovani A. Immunity. 2013; 1003-1018 3. Ridker PM, Everett BM, Thuren T, MacFadyen JG, et al. N Engl J Med. 2017 Aug 27.