Cutting edge: Negative regulation of dendritic cells through acetylation of the nonhistone protein STAT-3
Yaping Sun, Y Eugene Chin, Elizabeth Weisiger, Chelsea Malter, Isao Tawara, Tomomi Toubai, Erin Gatza, Paolo Mascagni, Charles A Dinarello, Pavan Reddy, Yaping Sun, Y Eugene Chin, Elizabeth Weisiger, Chelsea Malter, Isao Tawara, Tomomi Toubai, Erin Gatza, Paolo Mascagni, Charles A Dinarello, Pavan Reddy
Abstract
Histone deacetylase (HDAC) inhibition modulates dendritic cell (DC) functions and regulates experimental graft-vs-host disease and other immune-mediated diseases. The mechanisms by which HDAC inhibition modulates immune responses remain largely unknown. STAT-3 is a transcription factor shown to negatively regulate DC functions. In this study we report that HDAC inhibition acetylates and activates STAT-3, which regulates DCs by promoting the transcription of IDO. These findings demonstrate a novel functional role for posttranslational modification of STAT-3 through acetylation and provide mechanistic insights into HDAC inhibition-mediated immunoregulation by induction of IDO.
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Source: PubMed