Transcriptional profiling identifies Id2 function in dendritic cell development.
Dendritic cells (DCs) are potent antigen-presenting cells with a pivotal role in antigen-specific immune responses. Here, we found that the helix-loop-helix transcription factor Id2 is up-regulated during DC development in vitro and crucial for the development of distinct DC subsets in vivo. Id2-/- mice lack Langerhans cells (LCs), the cutaneous contingent of DCs, and the splenic CD8alpha+ DC subset is markedly reduced. Mice deficient for transforming growth factor (TGF)-beta also lack LCs, and we demonstrate here that, in DCs, TGF-beta induces Id2 expression. We also show that Id2 represses B cell genes in DCs. These findings reveal a TGF-beta-Id2 signaling pathway in DCs and suggest a mechanism by which Id2 affects the lineage choice of B cell and DC progenitors.
Hacker
Christine
C
Max-Delbrück-Center for Molecular Medicine, MDC, Robert-Rössle-Str. 10, 13092 Berlin, Germany.
Kirsch
Ralf D
RD
Ju
Xin-Sheng
XS
Hieronymus
Thomas
T
Gust
Tatjana C
TC
Kuhl
Christiane
C
Jorgas
Thorsten
T
Kurz
Steffen M
SM
Rose-John
Stefan
S
Yokota
Yoshifumi
Y
Zenke
Martin
M
D001402:B-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2; D020411:Oligonucleotide Array Sequence Analysis; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D019948:Receptors, Interleukin-4; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta