title: Type I interferons produced by dendritic cells promote their phenotypic and functional activation.
abstract: Resting dendritic cells (DCs) are resident in most tissues and can be activated by environmental stimuli to mature into potent antigen-presenting cells. One important stimulus for DC activation is infection; DCs can be triggered through receptors that recognize microbial components directly or by contact with infection-induced cytokines. We show here that murine DCs undergo phenotypic maturation upon exposure to type I interferons (type I IFNs) in vivo or in vitro. Moreover, DCs either derived from bone marrow cells in vitro or isolated from the spleens of normal animals express IFN-alpha and IFN-beta, suggesting that type I IFNs can act in an autocrine manner to activate DCs. Consistent with this idea, the ability to respond to type I IFN was required for the generation of fully activated DCs from bone marrow precursors, as DCs derived from the bone marrow of mice lacking a functional receptor for type I IFN had reduced expression of costimulatory and adhesion molecules and a diminished ability to stimulate naive T-cell proliferation compared with DCs derived from control bone marrow. Furthermore, the addition of neutralizing anti-IFN-alpha/beta antibody to purified splenic DCs in vitro partially blocked the "spontaneous" activation of these cells, inhibiting the up-regulation of costimulatory molecules, secretion of IFN-gamma, and T-cell stimulatory activity. These results show that DCs both secrete and respond to type I IFN, identifying type I interferons as autocrine DC activators.
authors.affiliation: Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Montoya
authors.forename: Giovanna
authors.initials: G
authors.lastname: Schiavoni
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mattei
authors.forename: Ion
authors.initials: I
authors.lastname: Gresser
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.forename: David F
authors.initials: DF
authors.lastname: Tough
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D019898:Autocrine Communication; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016130:Immunophenotyping; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017471:Receptors, Interferon / Q000235:genetics; D013154:Spleen / Q000166:cytology
chemical_list: D015703:Antigens, CD; D007370:Interferon Type I; D017471:Receptors, Interferon