title: Batf3 selectively determines acquisition of CD8+dendritic cell phenotype and function.
abstract: Batf3 is a transcription factor that impacts the development of CD103+tissue-resident dendritic cells (DCs). However, whether Batf3 is absolutely required for the development of CD8+DCs remains controversial. Id2 is required for CD8+DC development. Here we show that bone marrow chimeric mice with a deletion of Id2 in the CD11c compartment lose the ability to reject a skin graft expressing a non-self protein antigen or mount a delayed hypersensitivity response. In contrast, Batf3-/-mice remained competent for skin graft rejection and delayed hypersensitivity, and retained a CD8+DC population with markers characteristic of the CD11b+DC lineage, including CD11b, CD4 and CD172α, as well as the key regulator transcription factor IRF4, but lacked IRF8 expression. CD8+DCs in Batf3-/-mice took up and cleaved protein antigen and larger particles but were unable to phagocytose dying cells, a characteristic feature to the CD8+DC lineage. These data clarify a requirement for CD8+lineage DCs to induce effectors of neo-antigen-driven skin graft rejection, and improve our understanding of DC subtype commitment by demonstrating that in the absence of Batf3 CD8+DCs can change their fate and become CD11b+DCs.
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Queensland, Australia.
authors.forename: Janin
authors.initials: J
authors.lastname: Chandra
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Queensland, Australia.
authors.forename: Paula T Y
authors.initials: PT
authors.lastname: Kuo
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Queensland, Australia.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Hahn
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Queensland, Australia.
authors.forename: Ian H
authors.identifier: 0000-0002-8002-4680
authors.initials: IH
authors.lastname: Frazer
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D019070:Cell Lineage; D003713:Dendritic Cells / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology; D050835:Interferon Regulatory Factors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D010641:Phenotype; D012097:Repressor Proteins / Q000378:metabolism*; D016038:Skin Transplantation; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4
chemical_list: D000941:Antigens; D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; D050835:Interferon Regulatory Factors; D012097:Repressor Proteins; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4; C533289:SNFT protein, mouse