L2
Prostaglindin I2 Orchestrates Regulatory and Effector T Cell-Mediated Autoimmunity
Saturday, March 4, 2017: 2:15 PM
Rooms B213-B214 (Georgia World Congress Center, Building B)
Melissa H. Bloodworth, , , ,
Rationale: Tregs maintain tolerance and prevent autoimmune disease by inhibiting T cell activation. Prostacyclin I2 (PGI2) signaling through the I prostanoid (IP) receptor inhibits allergic airway inflammation, but it remains unknown whether PGI2 regulates Tregs and Treg-mediated inflammation. We investigated the role of PGI2 on autoimmune manifestations and on Treg Foxp3 expression, suppressive function, and polarization.

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.