Th9-Endothelial Crosstalk Promotes Cardiovascular Disease in Patients with Psoriasis
Principal Investigator: Daniella Schwartz, M.D.
Institution: University of Pittsburgh
Grant Mechanism: Translational Research Grant
Funding Amount: $200,000
Project Start Date: August 1, 2021
Project End Date: July 30, 2023
Status: Active
Keywords: Basic Science, Cardiovascular Disease, Immunology, Psoriasis
Project Summary:
Inflammatory cytokines are molecules that cells secrete to mount an immune response. When immune cells inappropriately produce cytokines, patients can develop autoimmune or inflammatory diseases. In psoriasis, inflammatory cytokines like interleukin-17A (IL-17A) and IL-23 promote inflammation in the skin, joints, and heart. Current cytokine-blocking therapies are very effective for psoriatic rash but do not work as well for symptoms outside the skin – including arthritis and cardiovascular disease. This leads us to believe that other cytokines contribute to psoriatic inflammation outside the skin. We found that T helper 9 (Th9) cells, which produce the inflammatory cytokine IL-9, are elevated in patients with psoriasis. Patients with psoriasis and heart disease have more Th9 cells than patients without heart disease, and Th9 cells are found inside diseased blood vessels in the heart. IL-9 causes dysfunction in the cells that line the blood vessel walls. We would like to study these findings in patients with psoriatic heart disease, and in mouse models of psoriatic heart disease. Ultimately, we would like to block IL-9 in order to prevent heart disease in patients with psoriasis.
Researcher Profile:
The Schwartz lab studies a cytokine called IL-9, which links allergic and rheumatic diseases through regulation of lymphocytes, eosinophils, and mucosal barrier function. Research in the Schwartz lab is focused on defining the regulation and biological functions of IL-9 in the context of autoimmune and autoinflammatory conditions. We also try to expand the spectrum of rheumatic diseases by studying rare inborn errors of immunity that link allergic, autoimmune, and autoinflammatory pathologies. This includes the monogenic disease haploinsufficiency of A20 (HA20), an inborn error of ubiquitination that can cause severe autoinflammation, autoimmunity, immunodeficiency, and clinical allergy.