# PPARgamma Modulates CD4+ T-Cell Differentiation and Allergic Inflammation in Allergic Rhinitis: A Potential Therapeutic Target

## TL;DR

This study shows that PPARgamma helps control immune cells involved in allergic rhinitis and could be a new treatment target.

## Contribution

The study reveals PPARgamma's role in modulating CD4+ T-cell subsets and allergic inflammation in allergic rhinitis.

## Key findings

- PPARgamma deficiency worsened allergic symptoms and reduced regulatory T cells in mice.
- PPARgamma agonists promoted Treg development and suppressed harmful T-cell responses.
- Nasal eosinophil infiltration increased in PPARgamma-deficient mice.

## Abstract

Objectives: Given the emerging role of peroxisome proliferator-activated receptor gamma (PPARgamma) in immune regulation and the increasing prevalence of allergic rhinitis (AR), we sought to understand how modulation of the PPARgamma pathway impacts the balance of CD4+ T-cell subsets, particularly regulatory T cells (Tregs) and T helper (TH)1, TH2, and TH17 cells, which are key players in the pathogenesis of AR. This knowledge is crucial for developing novel therapeutic strategies targeting the PPARgamma-CD4+ T-cell axis to manage AR more effectively. Methods: We used PPARgammaf/fLyz2-Cre mice for PPARgamma deletion. In an ovalbumin (OVA)-induced AR mouse model, PPARgamma+/-f/fLyz2-Cre mice were assessed for allergic symptoms, splenic Tregs, and nasal eosinophils. Additionally, the effects of a PPARgamma agonist on the polarization of naïve CD4+ T cells were examined. Results: PPARgamma+/-f/fLyz2-Cre mice showed worsened allergic symptoms, reduced splenic Tregs, and increased nasal mucosa eosinophilic infiltration. PPARgamma agonist treatment promoted naïve CD4+ T-cell polarization into Tregs and inhibited their differentiation into TH1, TH2, and TH17 subsets. Conclusions: Our findings indicate that PPARgamma plays a crucial role in regulating TH-cell subsets in AR. PPARgamma agonists could be a potential therapeutic strategy to mitigate allergic inflammation in AR by promoting Treg development and suppressing pathogenic TH-cell responses.