Batf3 and Id2 have a synergistic effect on Irf8-directed classical CD8α+ dendritic cell development

Hemant Jaiswal, Monika Kaushik, Rachid Sougrat, Monica Gupta, Anup Dey, Rohit Verma, Keiko Ozato, Prafullakumar B. Tailor

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Dendritic cells (DCs) are heterogeneous cell populations represented by different subtypes, each varying in terms of gene expression patterns and specific functions. Recent studies identified transcription factors essential for the development of different DC subtypes, yet molecular mechanisms for the developmental program and functions remain poorly understood. In this study, we developed and characterized a mouse DC progenitor-like cell line, designated DC9, from Irf8-/- bone marrow cells as a model for DC development and function. Expression of Irf8 in DC9 cells led to plasmacytoid DCs and CD8α+ DC-like cells, with a concomitant increase in plasmacytoid DC- and CD8α+ DC-specific gene transcripts and induction of type I IFNs and IL12p40 following TLR ligand stimulation. Irf8 expression in DC9 cells led to an increase in Id2 and Batf3 transcript levels, transcription factors shown to be important for the development of CD8α+ DCs. We show that, without Irf8 , expression of Id2 and Batf3 was not sufficient for directing classical CD8α+ DC development. When coexpressed with Irf8, Batf3 and Id2 had a synergistic effect on classical CD8α+ DC development. We demonstrate that Irf8 is upstream of Batf3 and Id2 in the classical CD8α+ DC developmental program and define the hierarchical relationship of transcription factors important for classical CD8α+ DC development.
Original languageEnglish (US)
Pages (from-to)5993-6001
Number of pages9
JournalThe Journal of Immunology
Volume191
Issue number12
DOIs
StatePublished - Nov 13 2013

ASJC Scopus subject areas

  • Medicine(all)

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