Bidirectional immunoregulation of calcineurin inhibitor tacrolimus on FOXP3 transcription?

Abstract

The imbalance between regulatory T cells (Treg) and effector T cells is important for maintaining of psoriasis vulgaris. FOXP3 is a master control transcription factor for the development and function of Tregs and is critical for transcriptional repression. Tacrolimus is effective in treatment of psoriasis vulgaris. Data show that tacrolimus has multiple impacts on FOXP3, but the exact pharmacological mechanism of tacrolimus on FOXP3 have yet to be elucidated. We herein suggest the bidirectional immunoregulation of tacrolimus on FOXP3. High concentration of tacrolimus renders the cooperation of NFAT with STAT6 and NF-κB to activate GATA3 transcription. On the contrary, low concentration of tacrolimus results in higher nucleus level of NFAT, which directly binds to FOXP3 enhancer and/or cooperates with Smad3 to activate FOXP3 transcription. Further studies using loss of function and over-expression methods are needed to determine the detailed molecules involved in this bidirectional immunoregulation of tacrolimus on FOXP3.

• Authors: Zhu Shen, Qiuhe Song, Ling Chen, Baiyu Zhong, Shuqian Tang, Fei Hao
• Journal: Medical hypotheses (Med Hypotheses) Vol. 76 Issue 2 Pg. 178-80 (Feb 2011) ISSN: 1532-2777 [Electronic] United States
• PMID: 20937549 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Calcineurin Inhibitors
• FOXP3 protein, human
• Forkhead Transcription Factors
• GATA3 Transcription Factor
• GATA3 protein, human
• Immunosuppressive Agents
• NFATC Transcription Factors
• STAT6 Transcription Factor
• STAT6 protein, human
• Transcription Factors
• Tacrolimus

Topics

• Animals
• Calcineurin Inhibitors
• Cell Nucleus (metabolism)
• Dose-Response Relationship, Drug
• Forkhead Transcription Factors (metabolism)
• GATA3 Transcription Factor (metabolism)
• Gene Expression Regulation
• Humans
• Immunosuppressive Agents (pharmacology)
• NFATC Transcription Factors (metabolism)
• Psoriasis (metabolism)
• STAT6 Transcription Factor (metabolism)
• T-Lymphocytes, Regulatory (metabolism)
• Tacrolimus (pharmacology)
• Transcription Factors (metabolism)