Abstract Number: OC 16.3
Meeting: ISTH 2021 Congress
Background: Regulatory T cells (Treg) suppress pathological immune responses, maintain tissue homeostasis and potentiate tissue repair after damage. While immunoregulatory Treg activities in lymphoid tissues have been extensively studied, little is known about Treg activities in non-lymphoid tissues and venous thrombosis has not been studied so far.
Aims: Elucidation of the phenotype, function and therapeutic benefit of Treg that accumulate in venous thrombi.
Methods: Mouse vena cava ligation model including re-ligation experiments, reporter and knockout mice, selective Treg depletion or expansion in vivo, adoptive transfer experiments, flow cytometry and flow-assisted cell sorting, bulk RNA-Seq and scRNA-Seq, Histology.
Results: 1) Treg accumulate in venous blood clots and determine the rate of thrombus resolution.
2) Clot-busting Treg control monocyte numbers and differentiation in resolving thrombi.
3) Clot Treg express a repair Treg cell profile and contain a distinct population that produces the matricellular Secreted protein acidic and rich in cysteine (SPARC) in response to inflammatory cytokines.
4) Treg-derived SPARC is critically needed in intra-thrombic monocyte fibrinolysis and differentiation.
5) Acceleration of thrombolysis by selective Treg expansion is only effective in the resolution phase.
Conclusions: A specialized population of SPARC+ clot Treg is critically needed in clot resorption and can be therapeutically exploited through IL-2-mediated Treg expansion.
To cite this abstract in AMA style:Shahneh F, Klein M, Frauhammer F, Probst HC, Schäfer K, K Raker V, Becker C. Specialized SPARC-forming Regulatory T Cells Control Venous Blood Clot Degradation [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/specialized-sparc-forming-regulatory-t-cells-control-venous-blood-clot-degradation/. Accessed September 25, 2021.
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