title: Compensatory dendritic cell development mediated by BATF-IRF interactions.
abstract: The AP1 transcription factor Batf3 is required for homeostatic development of CD8α(+) classical dendritic cells that prime CD8 T-cell responses against intracellular pathogens. Here we identify an alternative, Batf3-independent pathway in mice for CD8α(+) dendritic cell development operating during infection with intracellular pathogens and mediated by the cytokines interleukin (IL)-12 and interferon-γ. This alternative pathway results from molecular compensation for Batf3 provided by the related AP1 factors Batf, which also functions in T and B cells, and Batf2 induced by cytokines in response to infection. Reciprocally, physiological compensation between Batf and Batf3 also occurs in T cells for expression of IL-10 and CTLA4. Compensation among BATF factors is based on the shared capacity of their leucine zipper domains to interact with non-AP1 factors such as IRF4 and IRF8 to mediate cooperative gene activation. Conceivably, manipulating this alternative pathway of dendritic cell development could be of value in augmenting immune responses to vaccines.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.
authors.forename: Roxane
authors.initials: R
authors.lastname: Tussiwand
authors.forename: Wan-Ling
authors.initials: WL
authors.lastname: Lee
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.forename: Mona
authors.initials: M
authors.lastname: Mashayekhi
authors.forename: Wumesh
authors.initials: W
authors.lastname: KC
authors.forename: Jörn C
authors.initials: JC
authors.lastname: Albring
authors.forename: Ansuman T
authors.initials: AT
authors.lastname: Satpathy
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Rotondo
authors.forename: Brian T
authors.initials: BT
authors.lastname: Edelson
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Kretzer
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Wu
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Weiss
authors.forename: Elke
authors.initials: E
authors.lastname: Glasmacher
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Liao
authors.forename: Michael
authors.initials: M
authors.lastname: Behnke
authors.forename: Samuel S K
authors.initials: SS
authors.lastname: Lam
authors.forename: Cora T
authors.initials: CT
authors.lastname: Aurthur
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
authors.forename: Harinder
authors.initials: H
authors.lastname: Singh
authors.forename: Christina L
authors.initials: CL
authors.lastname: Stallings
authors.forename: L David
authors.initials: LD
authors.lastname: Sibley
authors.forename: Robert D
authors.initials: RD
authors.lastname: Schreiber
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D039001:Integrin alpha Chains / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D016350:Leucine Zippers; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D016759:Oncogene Protein p65(gag-jun) / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4
chemical_list: D015703:Antigens, CD; D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; D060908:CTLA-4 Antigen; D039001:Integrin alpha Chains; D050835:Interferon Regulatory Factors; D016753:Interleukin-10; D018664:Interleukin-12; D016759:Oncogene Protein p65(gag-jun); D012097:Repressor Proteins; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4; C576672:BATF2 protein, mouse; C431772:Batf protein, mouse; C556707:Ctla4 protein, mouse; C533289:SNFT protein, mouse; C091367:alpha E integrins