For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells.

TitleContinuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells.
Publication TypeJournal Article
Year of Publication2010
AuthorsGhosh HS, Cisse B, Bunin A, Lewis KL, Reizis B
JournalImmunity
Volume33
Issue6
Pagination905-16
Date Published2010 Dec 14
ISSN1097-4180
KeywordsAnimals, Antigen Presentation, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cell Differentiation, Cell Lineage, Cell Separation, Cell Transdifferentiation, Cells, Cultured, Dendritic Cells, Flow Cytometry, Gene Expression Profiling, Gene Expression Regulation, Developmental, Mice, Mice, Inbred C57BL, Mice, Knockout, Transcription Factor 4
Abstract

The interferon-producing plasmacytoid dendritic cells (pDCs) share common progenitors with antigen-presenting classical dendritic cells (cDCs), yet they possess distinct morphology and molecular features resembling those of lymphocytes. It is unclear whether the unique cell fate of pDCs is actively maintained in the steady state. We report that the deletion of transcription factor E2-2 from mature peripheral pDCs caused their spontaneous differentiation into cells with cDC properties. This included the loss of pDC markers, increase in MHC class II expression and T cell priming capacity, acquisition of dendritic morphology, and induction of cDC signature genes. Genome-wide chromatin immunoprecipitation revealed direct binding of E2-2 to key pDC-specific and lymphoid genes, as well as to certain genes enriched in cDCs. Thus, E2-2 actively maintains the cell fate of mature pDCs and opposes the "default" cDC fate, in part through direct regulation of lineage-specific gene expression programs.

DOI10.1016/j.immuni.2010.11.023
Alternate JournalImmunity
PubMed ID21145760
PubMed Central IDPMC3010277
Grant ListR01 AI072571-01A1 / AI / NIAID NIH HHS / United States
R01 AI072571-02 / AI / NIAID NIH HHS / United States
F31 AI080184 / AI / NIAID NIH HHS / United States
AI072571 / AI / NIAID NIH HHS / United States
T32 GM007367 / GM / NIGMS NIH HHS / United States
R01 AI072571-02S1 / AI / NIAID NIH HHS / United States
AI072571-S1 / AI / NIAID NIH HHS / United States
AI007161 / AI / NIAID NIH HHS / United States
T32 AI007161 / AI / NIAID NIH HHS / United States
AI080184 / AI / NIAID NIH HHS / United States
R01 AI072571 / AI / NIAID NIH HHS / United States
R21 AI085439-01 / AI / NIAID NIH HHS / United States
R21 AI085439 / AI / NIAID NIH HHS / United States
GM007367 / GM / NIGMS NIH HHS / United States
R01 AI072571-03 / AI / NIAID NIH HHS / United States
AI085439 / AI / NIAID NIH HHS / United States