Visual Universitätsmedizin Mainz

TRP X25 - Protease-mediated Functional Tuning of ‘Clot-busting’ Regulatory T cells

Funding period: 01.01.2019 – 30.06.2020

Project Summary

Regulatory T cells (Treg) have an important and non-redundant role in tissue repair - distinct from their role in suppression of immune responses. We recently identified a specialized population of resident ’repair Treg’ that develops in venous thrombi, is activated by inflammatory mediators, and regulates thrombus resolution and remodeling. The cellular and molecular mechanisms underlying the development and function of ’clot-busting’ Treg are undefined.

Coagulation protease signaling through protease-activated receptors (PARs) plays an important immuno-modulatory role during inflammation and certain coagulation proteases have been reported to boost the immunosuppressive activity of Treg. The probable role of PAR-mediated signals in ’repair Treg’ function has, however, not been addressed. Preliminary data in a PAR2 mutant strain demonstrate an altered thrombus resolution associated with altered ‘clot-resolving’ Treg numbers. To identify PAR1/2 signals that influence ‘clot-resolving’ Treg activity we will analyze their numbers and phenotypes in six mouse lines, whose PAR1 or PAR2 molecules are insensitive to particular coagulation proteases. The proposed experiments support a project in a current CTH initiative. They address a fundamental new question and link basic research in hemostasis and immunology.

Principal Investigator

PD Becker, PhD
Christian Becker, PhD, PD
Position: Principal Investigator

06131 17-2917