Cutting edge: Negative regulation of dendritic cells through acetylation of the nonhistone protein STAT-3.
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.
Department of Internal Medicine and University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-0942, USA.
Yaping
Y
Sun
Y Eugene
YE
Chin
Elizabeth
E
Weisiger
Chelsea
C
Malter
Isao
I
Tawara
Tomomi
T
Toubai
Erin
E
Gatza
Paolo
P
Mascagni
Charles A
CA
Dinarello
Pavan
P
Reddy
D000107:Acetylation; D000818:Animals; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000187:drug effects; D047468:Immunoprecipitation; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism*
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D050796:STAT3 Transcription Factor; D006655:Histone Deacetylases