Background: Regulatory T cells (T_reg) suppress pathological immune responses, maintain tissue homeostasis and potentiate tissue repair after damage. While immunoregulatory T_reg activities in lymphoid tissues have been extensively studied, little is known about T_reg activities in non-lymphoid tissues and venous thrombosis has not been studied so far.

Aims: Elucidation of the phenotype, function and therapeutic benefit of T_reg that accumulate in venous thrombi.

Methods: Mouse vena cava ligation model including re-ligation experiments, reporter and knockout mice, selective T_reg depletion or expansion in vivo, adoptive transfer experiments, flow cytometry and flow-assisted cell sorting, bulk RNA-Seq and scRNA-Seq, Histology.

Results: 1) T_reg accumulate in venous blood clots and determine the rate of thrombus resolution.  
2) Clot-busting T_reg control monocyte numbers and differentiation in resolving thrombi.
3) Clot T_reg express a repair T_reg 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) T_reg-derived SPARC is critically needed in intra-thrombic monocyte fibrinolysis and differentiation.
5) Acceleration of thrombolysis by selective T_reg 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.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/specialized-sparc-forming-regulatory-t-cells-control-venous-blood-clot-degradation/