dc.contributor.author | MILLS, KINGSTON | en |
dc.contributor.author | DUNGAN, LEONORA | en |
dc.contributor.author | LYNCH, MARINA | en |
dc.date.accessioned | 2014-10-21T11:46:19Z | |
dc.date.available | 2014-10-21T11:46:19Z | |
dc.date.issued | 2014 | en |
dc.date.submitted | 2014 | en |
dc.identifier.citation | Dungan LS, McGuinness NC, Boon L, Lynch MA, Mills KH, Innate IFN-gamma promotes development of experimental autoimmune encephalomyelitis: A role for NK cells and M1 macrophages., European Journal of Immunology, 44, 10, 2014, 2903-17 | en |
dc.identifier.issn | 0014-2980 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/71662 | |
dc.description | PUBLISHED | en |
dc.description.abstract | The role of IFN-γ in the pathogenesis of autoimmune diseases is controversial. Although Th1 cells can induce experimental autoimmune encephalomyelitis (EAE), IFN-γ can suppress Th17 cells that are pathogenic in EAE. Here we show that NK cells provide an early source of IFN-γ during development of EAE. Depletion of NK cells or neutralization of IFN-γ delayed the onset of EAE and was associated with reduced infiltration of IL-17(+) and GM-CSF(+) T cells into the CNS. In the passive transfer model, immune cells from myelin oligodendrocyte glycoprotein (MOG)-immunized IFN-γ(-/-) mice failed to induce EAE, despite producing IL-17 and GM-CSF. The macrophages expressed markers of M2 activation and the T cells had low very late antigen-4 (VLA-4) expression and failed to infiltrate the CNS. Addition of recombinant IFN-γ to immune cells from the IFN-γ(-/-) mice activated M1 macrophages and restored VLA-4 expression, migratory, and encephalitogenic activity of T cells. Furthermore, treatment of recipient mice with anti-VLA-4 neutralizing antibody abrogated EAE induced by transfer of T cells from WT mice. Our findings demonstrate IFN-γ-producing T cells are not required for development of EAE, but NK cell-derived IFN-γ has a key role in promoting M1 macrophage expansion and VLA-4-mediated migration of encephalitogenic T cells into the CNS. | en |
dc.format.extent | 2903-17 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | European Journal of Immunology | en |
dc.relation.ispartofseries | 44 | en |
dc.relation.ispartofseries | 10 | en |
dc.rights | Y | en |
dc.subject | T cells | en |
dc.subject | NK cells | en |
dc.subject | Macrophage | en |
dc.subject | IFN-γ | en |
dc.subject | EAE | en |
dc.title | Innate IFN-gamma promotes development of experimental autoimmune encephalomyelitis: A role for NK cells and M1 macrophages. | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/millsk | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/lynchma | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/ldungan | en |
dc.identifier.rssinternalid | 95812 | en |
dc.identifier.doi | http://dx.doi.org/10.1002/eji.201444612 | en |
dc.rights.ecaccessrights | openAccess | |
dc.subject.TCDTheme | Immunology, Inflammation & Infection | en |
dc.identifier.rssuri | http://dx.doi.org/10.1002/eji.201 | en |
dc.identifier.orcid_id | 0000-0003-3646-8222 | en |