title: Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells.
abstract: Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8alpha+ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3(-/-) mice also lack CD103+CD11b- DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3(-/-) mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103+CD11b- DCs, with the population of CD103+CD11b+ DCs remaining intact. Batf3(-/-) mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103+ DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8alpha+ cDCs and nonlymphoid CD103+ DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ-resident CD8alpha+ cDCs and nonlymphoid CD103+ DCs.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Edelson
authors.forename: Wumesh
authors.initials: W
authors.lastname: KC
authors.forename: Richard
authors.initials: R
authors.lastname: Juang
authors.forename: Masako
authors.initials: M
authors.lastname: Kohyama
authors.forename: Loralyn A
authors.initials: LA
authors.lastname: Benoit
authors.forename: Paul A
authors.initials: PA
authors.lastname: Klekotka
authors.forename: Clara
authors.initials: C
authors.lastname: Moon
authors.forename: Jörn C
authors.initials: JC
authors.lastname: Albring
authors.forename: Wataru
authors.initials: W
authors.lastname: Ise
authors.forename: Drew G
authors.initials: DG
authors.lastname: Michael
authors.forename: Deepta
authors.initials: D
authors.lastname: Bhattacharya
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holtzman
authors.forename: Sun-Sang J
authors.initials: SS
authors.lastname: Sung
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.forename: Kai
authors.initials: K
authors.lastname: Hildner
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D016827:CD8 Antigens / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D039001:Integrin alpha Chains / Q000378:metabolism*; D050835:Interferon Regulatory Factors / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D008643:Mesentery / Q000166:cytology / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D010253:Respirovirus Infections / Q000276:immunology; D029082:Sendai virus / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics; D000099185:Interferon Regulatory Factor-8
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; D004139:Dinitrofluorobenzene; D039001:Integrin alpha Chains; D050835:Interferon Regulatory Factors; D016186:Receptor, Macrophage Colony-Stimulating Factor; D012097:Repressor Proteins; D014157:Transcription Factors; D051941:fms-Like Tyrosine Kinase 3; D000099185:Interferon Regulatory Factor-8; C409469:CD8 antigen, alpha chain; C533289:SNFT protein, mouse; C091367:alpha E integrins; C497971:Flt3 protein, mouse