Summary of Research

Identification of the mechanism of GPR174 in cardiac/pulmonary inflammation. G protein-coupled receptor 174 (GPR174) variation has been proposed to be a risk factor for Graves’s disease, autoimmune Addison’s diseaseand vasovagal syncope. GPR174 was found to be a receptor for lysophosphatidylserine (lysoPS) and was suggested to signal via Gα12/13-containing heterotrimeric G proteins. Studies on GPR174-deficient mice revealed a role for the receptor in restraining T regulatory (Treg) cell development and function and conventional T cell proliferation and IL-2 production. In another reports, signaling was suggested to occur via Gαs-containing heterotrimeric G proteins. Moreover, GPR174 was reported to support B cell migration to spleen stromal cell culture supernatants and biochemical fractionation led to the suggestion that CCL19 and CCL21, well-defined CCR7 ligands, were ligands for GPR174. These results indicate that the GPR174 plays an important role in immune response. However, the role of GPR174 in the immune response of heart failure and pulmonary injury is unclear.  And there is currently a lack of clear understanding regarding the signaling pathway(s) engaged downstream of GPR174. Therefore, our study aims to better understand the mechanism of GPR174 in Treg immune response in cardiac/pulmonary diseases.