title: CD8α+ DCs can be induced in the absence of transcription factors Id2, Nfil3, and Batf3.
abstract: Antiviral immunity and cross-presentation is mediated constitutively through CD8α+ and CD103+ DCs. Development of these DC subsets is thought to require the transcription factors Irf8, Id2, Nfil3, and Batf3, although how this network is regulated is poorly defined. We addressed the nature of the differentiation blocks observed in the absence of these factors and found that although all 4 factors are required for CD103+ DC development, only Irf8 is essential for CD8α+ DCs. CD8α+ DCs emerged in the absence of Id2, Nfil3 and Batf3 in short-term bone marrow reconstitution. These “induced” CD8α+ DCs exhibit several hallmarks of classic CD8α+ DCs including the expression of CD24, Tlr3, Xcr1, Clec9A, and the capacity to cross-present soluble, cell-associated antigens and viral antigens even in the absence of Batf3. Collectively, these results uncover a previously undescribed pathway by which CD8α+ DCs emerge independent of Id2, Nfil3, and Batf3, but dependent on Irf8.
authors.affiliation: Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Cyril
authors.initials: C
authors.lastname: Seillet
authors.forename: Jacob T
authors.initials: JT
authors.lastname: Jackson
authors.forename: Kate A
authors.initials: KA
authors.lastname: Markey
authors.forename: Hugh J M
authors.initials: HJ
authors.lastname: Brady
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Hill
authors.forename: Kelli P A
authors.initials: KP
authors.lastname: Macdonald
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016827:CD8 Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D018259:Herpesvirus 1, Human / Q000276:immunology; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000099185:Interferon Regulatory Factor-8
chemical_list: D000956:Antigens, Viral; D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; D051797:Inhibitor of Differentiation Protein 2; D050835:Interferon Regulatory Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8; C409469:CD8 antigen, alpha chain; C497452:Idb2 protein, mouse; C497441:Nfil3 protein, mouse; C533289:SNFT protein, mouse