Plastic downregulation of the transcriptional repressor BCL6 during maturation of human dendritic cells.
Dendritic cell (DC) maturation links peripheral events initiated by the encounter with pathogens to the activation and expansion of antigen-specific T lymphocytes in secondary lymphoid organs. Here, we describe an as yet unrecognized modulator of human DC maturation, the transcriptional repressor BCL6. We found that both myeloid and plasmacytoid DCs constitutively express BCL6, which is rapidly downregulated following maturation triggered by selected stimuli. Both in unstimulated and maturing DCs, control of BCL6 protein levels reflects the convergence of several mechanisms regulating BCL6 stability, mRNA transcription and nuclear export. By regulating the induction of several genes implicated in the immune response, including inflammatory cytokines, chemokines and survival genes, BCL6 may represent a pivotal modulator of the afferent branch of the immune response.
Pantano
Serafino
S
Institute for Research in Biomedicine, Via Vela 6, Bellinzona CH6500, Switzerland. serafino.pantano@unil.ch
Jarrossay
David
D
Saccani
Simona
S
Bosisio
Daniela
D
Natoli
Gioacchino
G
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D017951:Antigen Presentation / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015533:Transcriptional Activation / Q000235:genetics
C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D007155:Immunologic Factors; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D012097:Repressor Proteins