Specialized regulatory T cells control venous blood clot resolution through SPARC

The cells and mechanisms involved in blood clot resorption are only partially known. We show that regulatory T (Treg) cells 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), show that SPARC enhances monocyte MMP activity and that SPARC+ Treg are crucial for blood clot resorption. By comparing different treatment times, we define a therapeutic window of Treg expansion that accelerates clot resorption.