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Publication : Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells.

First Author  Kanada S Year  2011
Journal  Blood Volume  117
Issue  7 Pages  2211-22
PubMed ID  21119111 Mgi Jnum  J:169576
Mgi Id  MGI:4941297 Doi  10.1182/blood-2010-06-291898
Citation  Kanada S, et al. (2011) Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells. Blood 117(7):2211-22
abstractText  In this study, we investigated the role of a transcription factor, PU.1, in the regulation of CD80 and CD86 expression in dendritic cells (DCs). A chromatin immunoprecipitation assay revealed that PU.1 is constitutively bound to the CD80 and CD86 promoters in bone marrow-derived DCs. In addition, co-expression of PU.1 resulted in the transactivation of the CD80 and CD86 promoters in a reporter assay. The binding of PU.1 to cis-enhancing regions was confirmed by electromobility gel-shift assay. As expected, inhibition of PU.1 expression by short interfering RNA (siRNA) in bone marrow-derived DCs resulted in marked down-regulation of CD80 and CD86 expression. Moreover, overexpression of PU.1 in murine bone marrow-derived lineage-negative cells induced the expression of CD80 and CD86 in the absence of monocyte/DC-related growth factors and/or cytokines. Based on these results, we conclude that PU.1 is a critical factor for the expression of CD80 and CD86. We also found that subcutaneous injection of PU.1 siRNA or topical application of a cream-emulsified PU.1 siRNA efficiently inhibited murine contact hypersensitivity. Our results suggest that PU.1 is a potential target for the treatment of immune-related diseases.
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