Specialized regulatory T cells control venous blood clot resolution through SPARC
Fatemeh Zare Shahneh, Alexandra Grill, Matthias Klein, Felix Frauhammer, Tobias Bopp, Katrin Schäfer, Verena Raker, Christian Becker
Abstract
The cells and mechanisms involved in blood clot resorption are only partially known. We show that regulatory T cells (Tregs) accumulate in venous blood clots and regulate thrombolysis by controlling the recruitment, differentiation and matrix metalloproteinase (MMP) activity of monocytes. We describe a clot Treg population that forms the matricellular acid- and cysteine-rich protein SPARC (secreted protein acidic and rich in cysteine) and show that SPARC enhances monocyte MMP activity and that SPARC+ Tregs are crucial for blood clot resorption. By comparing different treatment times, we define a therapeutic window of Treg expansion that accelerates clot resorption.