The function of LRRC32 in thrombosis, haemostasis and regulatory T cell homeostasis

Defects in blood platelet receptors often give rise to severe pathologies such as myocardial infarction or bleeding disorders. Therefore, significant efforts are put in the identification of new platelet receptors, with the Leucine Rich Repeat-Containing protein 32 (LRRC32) recently emerging. Next, the function of these receptors has in platelet physiology and thrombosis to be identified and  their potential as predictive marker and as target for the development of novel anti-thrombotics must be validated.

Besides its role in platelets, LRRC32 has been highlighted as a selective marker  (binding latent TGF-β) for activated regulatory T cells (Treg) that have a prominent role in the prevention of autoimmune disease and are associated to many pathological conditions. The intracellular transcription factor FOXP3 is currently used to characterize Treg although FOXP3 expression is not strictly restricted Treg only.

This project aims to determine the function of LRRC32 in both platelet physiology and Treg homeostasis. For this purpose, generic tools need to be developed. At first, LRRC32 knockout mice will be generated for in vivo models of thrombosis, stroke and bleeding. Additionally, Treg dependent disease models (experimental glioma) will be performed in these KO mice. Secondly, monoclonal antibodies will be produced for detection assays and functional testing that further can serve as a starting point for therapeutic applications. Thirdly, the link between FoxP3, LRRC32, TGF-β and platelet or Treg functionality will be explored using FOXP3 mutant mice and blood from FOXP3 deficient IPEX patients.