| 研究実績の概要 |
The major goal of this research project was to understand how Runx transcription factor complexes regulate CC chemokine CCL5 which plays many important roles in numerous infectious diseases as well as several cancers. In the previous years, I have generated several transgenic mouse lines with which I studied dynamic expression patterns of CCL5 by our immune system. To further decipher the precise molecular mechanisms behind the complicated expression patterns of CCL5, I proposed and generated two mouse lines in which distinctive Runx-binding sites around CCL5 gene were removed by Crispr/Cas9 system. By using these newly constructed mice, I have successfully identified two unique transcriptional enhancers which are required to tightly control CCL5 expression. Removing either of enhancer from mice, CCL5 expression was lost in specific stages of immune responses, indicating that these two enhancers confer the stage-specificities of CCL5. This discovery that CCL5 uses novel two-enhancer system will advance our understanding on CC chemokine regulation. Furthermore, I have found that controlled expression of CCL5 is indeed crucial to some specific aspects of our immune system and disease.
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