Methods: Whole animal histopathology was performed on aged WT and IP KO mice. Splenic T cells from WT and IP KO mice were enriched by magnetic selection and subsequently purified by FACS. For Treg suppression assays, Treg and CFSE-stained Teff were stimulated with anti-CD3 and anti-CD28. Induced Tregs (iTregs) were generated from CD4+ T cells by treating with immobilized anti-CD3 in the presence of IL-2 and TGF-β.
Results: PGI2 protected against autoimmune manifestations including splenomegaly, perivascular-bronchiolar lymphocytic cuffing, and epicarditis that developed in aged IP KO mice. PGI2 increased Treg Foxp3 expression, suppressive function, and polarization. PGI2 also increased Teff proliferation and susceptibility to Treg-mediated suppression.
Conclusions: PGI2 promotes Treg stability, suppressive function, and polarization. PGI2 simultaneously promotes Teff proliferation and susceptibility to Treg- mediated suppression. There is extensive interest in the application of Tregs in transplantation, autoimmune diseases, and allergy. PGI2 protects against autoimmunity and may represent a novel treatment strategy for Treg-mediated diseases.