Batf3 and Id2 have a synergistic effect on Irf8-directed classical CD8α+ dendritic cell development.
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.
Laboratory of Innate Immunity, National Institute of Immunology, New Delhi 110067, India;
Hemant
H
Jaiswal
Monika
M
Kaushik
Rachid
R
Sougrat
Monica
M
Gupta
Anup
A
Dey
Rohit
R
Verma
Keiko
K
Ozato
Prafullakumar
P
Tailor
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003712:Dendrites / Q000648:ultrastructure; D003713:Dendritic Cells / Q000737:chemistry / Q000145:classification / Q000166:cytology* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D051797:Inhibitor of Differentiation Protein 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050835:Interferon Regulatory Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic; D000099185:Interferon Regulatory Factor-8
D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; D051797:Inhibitor of Differentiation Protein 2; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; D053762:Interleukin-12 Subunit p40; D008565:Membrane Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D000099185:Interferon Regulatory Factor-8; C409469:CD8 antigen, alpha chain; C497452:Idb2 protein, mouse; C533289:SNFT protein, mouse; C084881:flt3 ligand protein