title: Astrocytes as antigen-presenting cells: expression of IL-12/IL-23.
abstract: Interleukin-12 (IL-12, p70) a heterodimeric cytokine of p40 and p35 subunits, important for Th1-type immune responses, has been attributed a prominent role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Recently, the related heterodimeric cytokine, IL-23, composed of the same p40 subunit as IL-12 and a unique p19 subunit, was shown to be involved in Th1 responses and EAE. We investigated whether astrocytes and microglia, CNS cells with antigen-presenting cell (APC) function can present antigen to myelin basic protein (MBP)-reactive T cells, and whether this presentation is blocked with antibodies against IL-12/IL-23p40. Interferon (IFN)-gamma-treated APC induced proliferation of MBP-reactive T cells. Anti-IL-12/IL-23p40 antibodies blocked this proliferation. These results support and extend our previous observation that astrocytes and microglia produce IL-12/IL-23p40. Moreover, we show that stimulated astrocytes and microglia produce biologically active IL-12p70. Because IL-12 and IL-23 share p40, we wanted to determine whether astrocytes also express IL-12p35 and IL-23p19, as microglia were already shown to express them. Astrocytes expressed IL-12p35 mRNA constitutively, and IL-23 p19 after stimulation. Thus, astrocytes, under inflammatory conditions, express all subunits of IL-12/IL-23. Their ability to present antigen to encephalitogenic T cells can be blocked by neutralizing anti-IL-12/IL-23p40 antibodies.
authors.affiliation: Division of Clinical Neurology, University Hospital, Queen's Medical Centre, Nottingham, UK. cris.constantinescu@nottingham.ac.uk
authors.forename: Cris S
authors.initials: CS
authors.lastname: Constantinescu
authors.forename: Marie
authors.initials: M
authors.lastname: Tani
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.forename: Maria
authors.initials: M
authors.lastname: Wysocka
authors.forename: Brendan
authors.initials: B
authors.lastname: Hilliard
authors.forename: Toshiki
authors.initials: T
authors.lastname: Fujioka
authors.forename: Sean
authors.initials: S
authors.lastname: Murphy
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Tighe
authors.forename: Jayasri
authors.initials: J
authors.lastname: Das Sarma
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000502:physiology*; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D009457:Neuroglia / Q000276:immunology / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
chemical_list: C508841:Il23a protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D004676:Myelin Basic Protein; D018664:Interleukin-12