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The transcriptional repressor Gfi1 controls STAT3-dependent dendritic cell development and function.

Chozhavendan Rathinam·Robert Geffers·Raif Yücel·Jan Buer·Karl Welte·Tarik Möröy·Christoph Klein
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Abstract

The mechanisms controlling the differentiation of dendritic cells (DCs) remain largely unknown. Using a transcriptional profiling approach, we identified Gfi1 as a novel critical transcription factor in DC differentiation. Gfi1-/- mice showed a global reduction of myeloid and lymphoid DCs in all lymphoid organs whereas epidermal Langerhans cells were enhanced in number. In vivo, Gfi1-/- DCs showed striking phenotypic and functional alterations such as defective maturation and increased cytokine production. In vitro, Gfi1-/- hematopoietic progenitor cells were unable to develop into DCs. Instead, they differentiated into macrophages, suggesting that Gfi1 is a critical modulator of DC versus macrophage development. Analysis of hematopoietic chimeras and retrovirus-reconstituted hematopoietic progenitor cells established a cell autonomous and nonredundant role for Gfi1 in DC development. The developmental defect of Gfi1-/- progenitor cells was associated with decreased STAT3 activation. In conclusion, we have identified Gfi1 as a critical transcription factor that controls DC versus macrophage development and dissociates DC maturation and activation.

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AnimalsCell DifferentiationDNA-Binding ProteinsDendritic CellsGene Expression ProfilingHematopoietic Stem CellsMacrophagesMiceSTAT3 Transcription FactorTrans-ActivatorsTranscription FactorsTranscription, GeneticJournal ArticleResearch Support, Non-U.S. Gov't

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Chozhavendan Rathinam, Robert Geffers, Raif Yücel, Jan Buer, Karl Welte, Tarik Möröy, Christoph Klein. 2005. The transcriptional repressor Gfi1 controls STAT3-dependent dendritic cell development and function.. https://doi.org/10.1016/j.immuni.2005.04.007

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