title: A single subset of dendritic cells controls the cytokine bias of natural killer T cell responses to diverse glycolipid antigens.
abstract: Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α(+) DEC-205(+) dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α(+) dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Pooja
authors.initials: P
authors.lastname: Arora
authors.affiliation: Grupo de Inmunología Celular e Inmunogenética GICIG, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No.52-21, Medellin 05001000, Colombia.
authors.forename: Andres
authors.initials: A
authors.lastname: Baena
authors.affiliation: Pediatric Infectious Diseases, Comer Children's Hospital, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Karl O A
authors.initials: KO
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Neeraj K
authors.initials: NK
authors.lastname: Saini
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Shalu S
authors.initials: SS
authors.lastname: Kharkwal
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Goldberg
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Shajo
authors.initials: S
authors.lastname: Kunnath-Velayudhan
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Millennium Institute on Immunology and Immunotherapy, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile.
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Carreño
authors.affiliation: National Institute of Mental Health and Neuroscience, Bangalore, Karnataka 560029, India.
authors.forename: Manjunatha M
authors.initials: MM
authors.lastname: Venkataswamy
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Eszter
authors.initials: E
authors.lastname: Lazar-Molnar
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Gregoire
authors.initials: G
authors.lastname: Lauvau
authors.affiliation: Department of Chemistry and Medicinal Chemistry Programme, National University of Singapore, and Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A(∗)STAR), Biopolis 117543, Singapore.
authors.forename: Young-tae
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Chemistry and Biochemistry, Queens College of CUNY, Flushing, NY 11367, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Biochemistry, Queens College of CUNY, Flushing, NY 11367, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bittman
authors.affiliation: Faculty of Medicine, Cancer Sciences Academic Unit, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: Aymen
authors.initials: A
authors.lastname: Al-Shamkhani
authors.affiliation: School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Liam R
authors.initials: LR
authors.lastname: Cox
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Jervis
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Natacha
authors.initials: N
authors.lastname: Veerapen
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: g.besra@bham.ac.uk.
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: steven.porcelli@einstein.yu.edu.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D055610:Antigens, CD1d / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002450:Cell Communication; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D005699:Galactosylceramides / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006706:Homeostasis; D007249:Inflammation / Q000276:immunology; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D055611:Natural Killer T-Cells / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D000941:Antigens; D015703:Antigens, CD; D055610:Antigens, CD1d; D016827:CD8 Antigens; C431698:CD8alpha antigen; D016207:Cytokines; C093569:DEC-205 receptor; D005699:Galactosylceramides; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; C493154:alpha-galactosylceramide