<i>PPARgamma</i> Modulates CD4<sup>+</sup> T-Cell Differentiation and Allergic Inflammation in Allergic Rhinitis: A Potential Therapeutic Target
<b>Objectives:</b> Given the emerging role of peroxisome proliferator-activated receptor gamma (<i>PPARgamma</i>) in immune regulation and the increasing prevalence of allergic rhinitis (AR), we sought to understand how modulation of the <i>PPARgamma</i> pathway i...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/7/1616 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849239902391107584 |
|---|---|
| author | Xiaoqing Rui Suyu Ruan Yu Zhang Ranran Fu Pengfei Sun Danzeng Lamu Weihua Wang |
| author_facet | Xiaoqing Rui Suyu Ruan Yu Zhang Ranran Fu Pengfei Sun Danzeng Lamu Weihua Wang |
| author_sort | Xiaoqing Rui |
| collection | DOAJ |
| description | <b>Objectives:</b> Given the emerging role of peroxisome proliferator-activated receptor gamma (<i>PPARgamma</i>) in immune regulation and the increasing prevalence of allergic rhinitis (AR), we sought to understand how modulation of the <i>PPARgamma</i> pathway impacts the balance of CD4<sup>+</sup> 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 <i>PPARgamma</i>-CD4<sup>+</sup> T-cell axis to manage AR more effectively. <b>Methods:</b> We used <i>PPARgamma</i><sup>f/f</sup>Lyz2-Cre mice for <i>PPARgamma</i> deletion. In an ovalbumin (OVA)-induced AR mouse model, <i>PPARgamma<sup>+/-f/f</sup>Lyz2</i>-Cre mice were assessed for allergic symptoms, splenic Tregs, and nasal eosinophils. Additionally, the effects of a <i>PPARgamma</i> agonist on the polarization of naïve CD4<sup>+</sup> T cells were examined. <b>Results:</b> <i>PPARgamma<sup>+/-f/f</sup>Lyz2</i>-Cre mice showed worsened allergic symptoms, reduced splenic Tregs, and increased nasal mucosa eosinophilic infiltration. <i>PPARgamma</i> agonist treatment promoted naïve CD4<sup>+</sup> T-cell polarization into Tregs and inhibited their differentiation into TH1, TH2, and TH17 subsets. <b>Conclusions:</b> Our findings indicate that <i>PPARgamma</i> plays a crucial role in regulating TH-cell subsets in AR. <i>PPARgamma</i> agonists could be a potential therapeutic strategy to mitigate allergic inflammation in AR by promoting Treg development and suppressing pathogenic TH-cell responses. |
| format | Article |
| id | doaj-art-9fe7b61257ad4d01a8913f859142e9ad |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-9fe7b61257ad4d01a8913f859142e9ad2025-08-20T04:00:49ZengMDPI AGBiomedicines2227-90592025-07-01137161610.3390/biomedicines13071616<i>PPARgamma</i> Modulates CD4<sup>+</sup> T-Cell Differentiation and Allergic Inflammation in Allergic Rhinitis: A Potential Therapeutic TargetXiaoqing Rui0Suyu Ruan1Yu Zhang2Ranran Fu3Pengfei Sun4Danzeng Lamu5Weihua Wang6Department of Otolaryngology-Head and Neck Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China<b>Objectives:</b> Given the emerging role of peroxisome proliferator-activated receptor gamma (<i>PPARgamma</i>) in immune regulation and the increasing prevalence of allergic rhinitis (AR), we sought to understand how modulation of the <i>PPARgamma</i> pathway impacts the balance of CD4<sup>+</sup> 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 <i>PPARgamma</i>-CD4<sup>+</sup> T-cell axis to manage AR more effectively. <b>Methods:</b> We used <i>PPARgamma</i><sup>f/f</sup>Lyz2-Cre mice for <i>PPARgamma</i> deletion. In an ovalbumin (OVA)-induced AR mouse model, <i>PPARgamma<sup>+/-f/f</sup>Lyz2</i>-Cre mice were assessed for allergic symptoms, splenic Tregs, and nasal eosinophils. Additionally, the effects of a <i>PPARgamma</i> agonist on the polarization of naïve CD4<sup>+</sup> T cells were examined. <b>Results:</b> <i>PPARgamma<sup>+/-f/f</sup>Lyz2</i>-Cre mice showed worsened allergic symptoms, reduced splenic Tregs, and increased nasal mucosa eosinophilic infiltration. <i>PPARgamma</i> agonist treatment promoted naïve CD4<sup>+</sup> T-cell polarization into Tregs and inhibited their differentiation into TH1, TH2, and TH17 subsets. <b>Conclusions:</b> Our findings indicate that <i>PPARgamma</i> plays a crucial role in regulating TH-cell subsets in AR. <i>PPARgamma</i> agonists could be a potential therapeutic strategy to mitigate allergic inflammation in AR by promoting Treg development and suppressing pathogenic TH-cell responses.https://www.mdpi.com/2227-9059/13/7/1616allergic rhinitis<i>PPARgamma</i>naïve CD4<sup>+</sup> T cellsregulatory T cellsT helper cells |
| spellingShingle | Xiaoqing Rui Suyu Ruan Yu Zhang Ranran Fu Pengfei Sun Danzeng Lamu Weihua Wang <i>PPARgamma</i> Modulates CD4<sup>+</sup> T-Cell Differentiation and Allergic Inflammation in Allergic Rhinitis: A Potential Therapeutic Target Biomedicines allergic rhinitis <i>PPARgamma</i> naïve CD4<sup>+</sup> T cells regulatory T cells T helper cells |
| title | <i>PPARgamma</i> Modulates CD4<sup>+</sup> T-Cell Differentiation and Allergic Inflammation in Allergic Rhinitis: A Potential Therapeutic Target |
| title_full | <i>PPARgamma</i> Modulates CD4<sup>+</sup> T-Cell Differentiation and Allergic Inflammation in Allergic Rhinitis: A Potential Therapeutic Target |
| title_fullStr | <i>PPARgamma</i> Modulates CD4<sup>+</sup> T-Cell Differentiation and Allergic Inflammation in Allergic Rhinitis: A Potential Therapeutic Target |
| title_full_unstemmed | <i>PPARgamma</i> Modulates CD4<sup>+</sup> T-Cell Differentiation and Allergic Inflammation in Allergic Rhinitis: A Potential Therapeutic Target |
| title_short | <i>PPARgamma</i> Modulates CD4<sup>+</sup> T-Cell Differentiation and Allergic Inflammation in Allergic Rhinitis: A Potential Therapeutic Target |
| title_sort | i ppargamma i modulates cd4 sup sup t cell differentiation and allergic inflammation in allergic rhinitis a potential therapeutic target |
| topic | allergic rhinitis <i>PPARgamma</i> naïve CD4<sup>+</sup> T cells regulatory T cells T helper cells |
| url | https://www.mdpi.com/2227-9059/13/7/1616 |
| work_keys_str_mv | AT xiaoqingrui ippargammaimodulatescd4supsuptcelldifferentiationandallergicinflammationinallergicrhinitisapotentialtherapeutictarget AT suyuruan ippargammaimodulatescd4supsuptcelldifferentiationandallergicinflammationinallergicrhinitisapotentialtherapeutictarget AT yuzhang ippargammaimodulatescd4supsuptcelldifferentiationandallergicinflammationinallergicrhinitisapotentialtherapeutictarget AT ranranfu ippargammaimodulatescd4supsuptcelldifferentiationandallergicinflammationinallergicrhinitisapotentialtherapeutictarget AT pengfeisun ippargammaimodulatescd4supsuptcelldifferentiationandallergicinflammationinallergicrhinitisapotentialtherapeutictarget AT danzenglamu ippargammaimodulatescd4supsuptcelldifferentiationandallergicinflammationinallergicrhinitisapotentialtherapeutictarget AT weihuawang ippargammaimodulatescd4supsuptcelldifferentiationandallergicinflammationinallergicrhinitisapotentialtherapeutictarget |