title: Existence of CD8α-like dendritic cells with a conserved functional specialization and a common molecular signature in distant mammalian species.
abstract: The mouse lymphoid organ-resident CD8alpha(+) dendritic cell (DC) subset is specialized in Ag presentation to CD8(+) T cells. Recent evidence shows that mouse nonlymphoid tissue CD103(+) DCs and human blood DC Ag 3(+) DCs share similarities with CD8alpha(+) DCs. We address here whether the organization of DC subsets is conserved across mammals in terms of gene expression signatures, phenotypic characteristics, and functional specialization, independently of the tissue of origin. We study the DC subsets that migrate from the skin in the ovine species that, like all domestic animals, belongs to the Laurasiatheria, a distinct phylogenetic clade from the supraprimates (human/mouse). We demonstrate that the minor sheep CD26(+) skin lymph DC subset shares significant transcriptomic similarities with mouse CD8alpha(+) and human blood DC Ag 3(+) DCs. This allowed the identification of a common set of phenotypic characteristics for CD8alpha-like DCs in the three mammalian species (i.e., SIRP(lo), CADM1(hi), CLEC9A(hi), CD205(hi), XCR1(hi)). Compared to CD26(-) DCs, the sheep CD26(+) DCs show 1) potent stimulation of allogeneic naive CD8(+) T cells with high selective induction of the Ifngamma and Il22 genes; 2) dominant efficacy in activating specific CD8(+) T cells against exogenous soluble Ag; and 3) selective expression of functional pathways associated with high capacity for Ag cross-presentation. Our results unravel a unifying definition of the CD8alpha(+)-like DCs across mammalian species and identify molecular candidates that could be used for the design of vaccines applying to mammals in general.
authors: Virologie et Immunologie Moléculaires UR892, Institut National de Recherche Agronomique, Domaine de Vilvert, Jouy-en-Josas, France.
authors: Vanessa
authors: V
authors: Contreras
authors: Céline
authors: C
authors: Urien
authors: Rachel
authors: R
authors: Guiton
authors: Yannick
authors: Y
authors: Alexandre
authors: Thien-Phong
authors: TP
authors: Vu Manh
authors: Thibault
authors: T
authors: Andrieu
authors: Karine
authors: K
authors: Crozat
authors: Luc
authors: L
authors: Jouneau
authors: Nicolas
authors: N
authors: Bertho
authors: Mathieu
authors: M
authors: Epardaud
authors: Jayne
authors: J
authors: Hope
authors: Ariel
authors: A
authors: Savina
authors: Sebastian
authors: S
authors: Amigorena
authors: Michel
authors: M
authors: Bonneau
authors: Marc
authors: M
authors: Dalod
authors: Isabelle
authors: I
authors: Schwartz-Cornil
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis* / Q000502:physiology; D002478:Cells, Cultured; D017124:Conserved Sequence; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007108:Immune Tolerance; D008196:Lymph / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D034561:Sheep, Domestic; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013045:Species Specificity
chemical_list: D016827:CD8 Antigens; C431698:CD8alpha antigen; D018819:Dipeptidyl Peptidase 4