title: The signal transducers STAT5 and STAT3 control expression of Id2 and E2-2 during dendritic cell development.
abstract: Cytokines and transcription factors play key roles in dendritic cell (DC) development, yet information about regulatory interactions between these signals remains limited. Here we show that the cytokines GM-CSF and Flt3L induce the transcriptional mediators Id2 and E2-2 and control DC lineage diversification by STAT-dependent pathways. We found that STAT5 is required for tissue CD103(+) DC generation and plasmacytoid DC (pDC) suppression in steady state or response to GM-CSF. STAT5 stimulates GM-CSF-dependent expression of Id2, which controls CD103(+) DC production and pDC inhibition. By contrast, pDCs, but not CD103(+) DCs, are dependent on STAT3. Consistently, STAT3 stimulates Flt3L-responsive expression of the pDC regulator Tcf4 (E2-2). These data suggest that STATs contribute to DC development by controlling transcription factors involved in lineage differentiation.
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Haiyan S
authors.initials: HS
authors.lastname: Li
authors.forename: Cliff Y
authors.initials: CY
authors.lastname: Yang
authors.forename: Kalyan C
authors.initials: KC
authors.lastname: Nallaparaju
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhang
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Ananda W
authors.initials: AW
authors.lastname: Goldrath
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Watowich
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000073940:Transcription Factor 4
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494087:Stat3 protein, mouse; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor