Fenofibrate Enhances the In Vitro Differentiation of Foxp3+ Regulatory T Cells in Mice
Foxp3+ regulatory T cells (Tregs) play a critical role in maintaining immune self-tolerance. Reduced number and activity of Tregs are usually found in autoimmune and inflammatory diseases, and enhancing the differentiation of Tregs may be a promising therapeutic strategy. Some reports suggested an a...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2012/529035 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832559376020275200 |
|---|---|
| author | Zhou Zhou Ying Liang Yanxiang Gao Wei Kong Juan Feng Xian Wang |
| author_facet | Zhou Zhou Ying Liang Yanxiang Gao Wei Kong Juan Feng Xian Wang |
| author_sort | Zhou Zhou |
| collection | DOAJ |
| description | Foxp3+ regulatory T cells (Tregs) play a critical role in maintaining immune self-tolerance. Reduced number and activity of Tregs are usually found in autoimmune and inflammatory diseases, and enhancing the differentiation of Tregs may be a promising therapeutic strategy. Some reports suggested an anti-inflammatory and anti-autoimmune potential for fenofibrate, a hypolipidemic drug used worldwide, whose lipid effects are mediated by the activation of peroxisome proliferator-activated receptor 𝛼 (PPAR𝛼). In the present paper, we found that fenofibrate dose-dependently increased transforming growth factor-𝛽 and interleukin-2-induced Treg differentiation in vitro, by 1.96-fold from 0 to 20 𝜇M (12.59±1.34% to 24.69±3.03%, 𝑃<0.05). Other PPAR𝛼 activators, WY14643 (100 𝜇M), gemfibrozil (50 𝜇M), and bezafibrate (30 𝜇M), could not enhance Treg differentiation. In addition, PPAR𝛼 could not upregulate the promoter activity of the Treg-specific transcription factor Foxp3. Fenofibrate might exert its function by enhancing Smad3 phosphorylation, a critical signal in Treg differentiation, via Akt suppression. Our work reveals a new PPAR𝛼 independent anti-inflammatory mechanism of fenofibrate in up-regulating mouse Treg differentiation. |
| format | Article |
| id | doaj-art-d2092a7c05b74075b0f6351c99ed38dd |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-d2092a7c05b74075b0f6351c99ed38dd2025-02-03T01:30:17ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/529035529035Fenofibrate Enhances the In Vitro Differentiation of Foxp3+ Regulatory T Cells in MiceZhou Zhou0Ying Liang1Yanxiang Gao2Wei Kong3Juan Feng4Xian Wang5Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, ChinaFoxp3+ regulatory T cells (Tregs) play a critical role in maintaining immune self-tolerance. Reduced number and activity of Tregs are usually found in autoimmune and inflammatory diseases, and enhancing the differentiation of Tregs may be a promising therapeutic strategy. Some reports suggested an anti-inflammatory and anti-autoimmune potential for fenofibrate, a hypolipidemic drug used worldwide, whose lipid effects are mediated by the activation of peroxisome proliferator-activated receptor 𝛼 (PPAR𝛼). In the present paper, we found that fenofibrate dose-dependently increased transforming growth factor-𝛽 and interleukin-2-induced Treg differentiation in vitro, by 1.96-fold from 0 to 20 𝜇M (12.59±1.34% to 24.69±3.03%, 𝑃<0.05). Other PPAR𝛼 activators, WY14643 (100 𝜇M), gemfibrozil (50 𝜇M), and bezafibrate (30 𝜇M), could not enhance Treg differentiation. In addition, PPAR𝛼 could not upregulate the promoter activity of the Treg-specific transcription factor Foxp3. Fenofibrate might exert its function by enhancing Smad3 phosphorylation, a critical signal in Treg differentiation, via Akt suppression. Our work reveals a new PPAR𝛼 independent anti-inflammatory mechanism of fenofibrate in up-regulating mouse Treg differentiation.http://dx.doi.org/10.1155/2012/529035 |
| spellingShingle | Zhou Zhou Ying Liang Yanxiang Gao Wei Kong Juan Feng Xian Wang Fenofibrate Enhances the In Vitro Differentiation of Foxp3+ Regulatory T Cells in Mice PPAR Research |
| title | Fenofibrate Enhances the In Vitro Differentiation of Foxp3+ Regulatory T Cells in Mice |
| title_full | Fenofibrate Enhances the In Vitro Differentiation of Foxp3+ Regulatory T Cells in Mice |
| title_fullStr | Fenofibrate Enhances the In Vitro Differentiation of Foxp3+ Regulatory T Cells in Mice |
| title_full_unstemmed | Fenofibrate Enhances the In Vitro Differentiation of Foxp3+ Regulatory T Cells in Mice |
| title_short | Fenofibrate Enhances the In Vitro Differentiation of Foxp3+ Regulatory T Cells in Mice |
| title_sort | fenofibrate enhances the in vitro differentiation of foxp3 regulatory t cells in mice |
| url | http://dx.doi.org/10.1155/2012/529035 |
| work_keys_str_mv | AT zhouzhou fenofibrateenhancestheinvitrodifferentiationoffoxp3regulatorytcellsinmice AT yingliang fenofibrateenhancestheinvitrodifferentiationoffoxp3regulatorytcellsinmice AT yanxianggao fenofibrateenhancestheinvitrodifferentiationoffoxp3regulatorytcellsinmice AT weikong fenofibrateenhancestheinvitrodifferentiationoffoxp3regulatorytcellsinmice AT juanfeng fenofibrateenhancestheinvitrodifferentiationoffoxp3regulatorytcellsinmice AT xianwang fenofibrateenhancestheinvitrodifferentiationoffoxp3regulatorytcellsinmice |