title: Id2 expression delineates differential checkpoints in the genetic program of CD8α+ and CD103+ dendritic cell lineages.
abstract: Dendritic cells (DCs) have critical roles in the induction of the adaptive immune response. The transcription factors Id2, Batf3 and Irf-8 are required for many aspects of murine DC differentiation including development of CD8α(+) and CD103(+) DCs. How they regulate DC subset specification is not completely understood. Using an Id2-GFP reporter system, we show that Id2 is broadly expressed in all cDC subsets with the highest expression in CD103(+) and CD8α(+) lineages. Notably, CD103(+) DCs were the only DC able to constitutively cross-present cell-associated antigens in vitro. Irf-8 deficiency affected loss of development of virtually all conventional DCs (cDCs) while Batf3 deficiency resulted in the development of Sirp-α(-) DCs that had impaired survival. Exposure to GM-CSF during differentiation induced expression of CD103 in Id2-GFP(+) DCs. It did not restore cross-presenting capacity to Batf3(-/-) or CD103(-)Sirp-α(-)DCs in vitro. Thus, Irf-8 and Batf3 regulate distinct stages in DC differentiation during the development of cDCs. Genetic mapping DC subset differentiation using Id2-GFP may have broad implications in understanding the interplay of DC subsets during protective and pathological immune responses.
authors.affiliation: Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
authors.forename: Jacob T
authors.initials: JT
authors.lastname: Jackson
authors.forename: Yifang
authors.initials: Y
authors.lastname: Hu
authors.forename: Ruijie
authors.initials: R
authors.lastname: Liu
authors.forename: Frederick
authors.initials: F
authors.lastname: Masson
authors.forename: Angela
authors.initials: A
authors.lastname: D'Amico
authors.forename: Sebastian
authors.initials: S
authors.lastname: Carotta
authors.forename: Annie
authors.initials: A
authors.lastname: Xin
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Camilleri
authors.forename: Adele M
authors.initials: AM
authors.lastname: Mount
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Smyth
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D018816:Genes, cdc / Q000502:physiology; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics* / Q000502:physiology; D039001:Integrin alpha Chains / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological
chemical_list: D015703:Antigens, CD; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D039001:Integrin alpha Chains; C091367:alpha E integrins