All-trans retinoic acid attenuates airway inflammation by inhibiting Th2 and Th17 response in experimental allergic asthma.

Abstract

BACKGROUND:

Airway inflammation is mainly mediated by T helper 2 cells (Th2) that characteristically produce interleukin (IL)-4, IL-5, and IL-13. Epidemiological studies have revealed an inverse association between the dietary intake of vitamin A and the occurrence of asthma. Serum vitamin A concentrations are significantly lower in asthmatic subjects than in healthy control subjects. It has been reported that all-trans retinoic acid (ATRA), a potent derivative of vitamin A, regulates immune responses. However, its role in Th2-mediated airway inflammation remains unclear. We investigated the effects of ATRA in a mouse model of allergic airway inflammation.

RESULTS:

We found that ATRA treatment attenuated airway inflammation and decreased mRNA levels of Th2- and Th17-related transcription factors. The data showed that airway inflammation coincided with levels of Th2- and Th17-related cytokines. We also showed that ATRA inhibited Th17 and promoted inducible regulatory T-cell differentiation, whereas it did not induce an obvious effect on Th2 differentiation in vitro. Our data suggest that ATRA may interfere with the in vivo Th2 responses via T-cell extrinsic mechanisms.

CONCLUSIONS:

Administration of ATRA dramatically attenuated airway inflammation by inhibiting Th2 and Th17 differentiation and/or functions. ATRA may have potential therapeutic effects for airway inflammation in asthmatic patients.

• Authors: Jinhong Wu, Yanjie Zhang, Qi Liu, Wenwei Zhong, Zhenwei Xia
• Journal: BMC immunology (BMC Immunol) Vol. 14 Pg. 28 (Jun 22 2013) ISSN: 1471-2172 [Electronic] England
• PMID: 23800145 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens
• Cytokines
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• Transcription Factors
• Tretinoin

Topics

• Animals
• Antigens (immunology)
• Asthma (complications, drug therapy, immunology, pathology)
• Cell Differentiation (drug effects)
• Cytokines (metabolism)
• Disease Models, Animal
• Down-Regulation (drug effects)
• Female
• Forkhead Transcription Factors (metabolism)
• Inflammation (drug therapy, genetics, immunology, pathology)
• Lung (drug effects, immunology, metabolism, pathology)
• Lymph Nodes (drug effects, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Spleen (drug effects, immunology, pathology)
• Th17 Cells (drug effects, immunology)
• Th2 Cells (drug effects, immunology)
• Transcription Factors (genetics, metabolism)
• Tretinoin (administration & dosage, pharmacology, therapeutic use)