title: NFIL3/E4BP4 is a key transcription factor for CD8α⁺ dendritic cell development.
abstract: Antigen presentation by mature dendritic cells (DCs) is the first step for initiating adaptive immune responses. DCs are composed of heterogeneous functional subsets; however, the molecular mechanisms that regulate differentiation of specific DC subsets are not understood. Here, we report that the basic leucine zipper transcription factor NFIL3/E4BP4 is essential for the development of CD8α(+) conventional DCs (cDCs). Nfil3(-/-) mice specifically lack CD8α(+) cDCs but not CD8α(-) cDCs or plasmacytoid DCs in lymphoid tissues. Flt3 ligand-dependent generation of CD8α(+) cDCs in lymphoid tissues and CD8α(+)-equivalent cDCs from Nfil3(-/-) bone marrow cells was also impaired. NFIL3 regulates CD8α(+) cDC development in part through Batf3 expression. Importantly, Nfil3(-/-) mice exhibited impaired cross-priming of CD8(+) T cells against cell-associated antigen, a process normally performed by CD8α(+) cDCs, and failed to produce IL-12 after TLR3 stimulation. Thus, NFIL3 plays an essential role in the development of CD8α(+) cDCs.
authors.affiliation: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kashiwada
authors.forename: Nhat-Long L
authors.initials: NL
authors.lastname: Pham
authors.forename: Lecia L
authors.initials: LL
authors.lastname: Pewe
authors.forename: John T
authors.initials: JT
authors.lastname: Harty
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rothman
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D008565:Membrane Proteins; C497441:Nfil3 protein, mouse; D012097:Repressor Proteins; C533289:SNFT protein, mouse; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; C084881:flt3 ligand protein; D018664:Interleukin-12