Prostaglandin I₂ signaling in Treg restrains ST2 expression and associated pathogenicity

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Presentation Time: 10:00 AM - 10:15 AM
Abstract ID: 4288 - B

Presenting Author:
Allison E Norlander , Assistant Professor at Indiana Univ. Purdue Univ. Indianapolis

Abstract:

We reported Prostaglandin I₂ (PGI₂) signaling within Treg is critical for Treg suppressive function in allergic airway inflammation (AAI). Interestingly, pathogenic Treg that have impaired suppressive capacity and promote AAI have greater ST2 expression. We hypothesized that Treg PGI₂ signaling limits ST2 expression via restraint of β-Catenin signaling in AAI to prevent Treg pathogenicity. The percentage of ST2+ Tregs was elevated at baseline in IP deficient (IP KO) Treg, which lack the receptor for PGI₂, compared to WT Treg. To further test our hypothesis, we utilized an Alternaria alternata (Alt) extract sensitization and challenge protocol. Alt-challenged mice that lacked IP signaling only on Treg (Foxp3^YFPcrexIP^flox) had elevated BAL IL-13, BAL eosinophils, lung vascular remodeling, and lung ST2+ Treg percentages compared to Foxp3^YFPcre controls. Moreover, there were elevated total lung ST2+IL13+ Treg and ex-Treg in Alt-challenged fate-mapping IP KO mice compared to fate-mapping controls. Interestingly, BAL IL-13, BAL eosinophils, lung ST2+ Treg percentages were significantly decreased in Alt-challenged mice that had Treg specific deficiency for both IP and β-Catenin (Foxp3^YFPcrexIP^floxxCtnnb1^flox) compared to Foxp3^YFPcrexIP^flox mice. In summary, we demonstrate an association of Treg ST2 expression with enhanced Treg pathogenicity in a mouse model of AAI in IP deficient Treg mediated by β-Catenin. These data support PGI₂ as a therapeutic for asthma.