Prostaglindin I2 Receptor (IP) Signaling Increases Regulatory T (Treg) Cell Induction and Function and Renders T Effector (Teff) Cells More Susceptible to Treg-Mediated Suppression
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Melissa H. Bloodworth, B.S., Kasia Goleniewska, M.S., R. Stokes Peebles Jr., MD FAAAAI
Rationale: Regulatory T (Treg) cells are pivotal in suppressing immune responses and maintaining tolerance. Prostacyclin I2 (PGI2) signaling through the I prostanoid (IP) receptor has anti-inflammatory effects and inhibits Th2-mediated cardinal features of asthma. We reported that PGI2 inhibits dendritic cell function and Th2 cytokine production; however, the effect of PGI2 on Treg cell function is not known. 

Methods: Naïve CD4+ T, Teff, and Treg cells were isolated from the spleens of BALB/c WT and IPKO mice. To induce iTreg differentiation, CD4+ cells were cultured with anti-CD3, IL-2 and TGF-B for 6 days. Treg and CFSE+ Teff were stimulated with anti-CD3 and anti-CD28 for 3 days. The percent inhibition was calculated as follows: [(proliferation at ratio/proliferation Teff only)*100].

Results: Naïve CD4+ cells from IPKO mice exhibited significantly decreased iTreg cell induction compared to naïve CD4+ cells from WT mice. There was a significant increase in splenic Treg cell numbers in IPKO mice compared to WT mice. Treg cells from IPKO mice had significantly decreased suppressive function compared to Treg cells from WT mice, and Teff cells from IPKO mice were less susceptible to Treg-mediated suppression compared to Teff cells from WT mice.

Conclusions: Endogenous PGI2-IP signaling increases iTreg cell induction and Treg cell function, and renders Teff cells more susceptible to Treg- mediated suppression. These results suggest a possible mechanism by which PGI2 inhibits airway inflammation during allergic asthma.