Innate IFN-gamma promotes development of experimental autoimmune encephalomyelitis: A role for NK cells and M1 macrophages.
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2014Access:
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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, 2903-17Download Item:
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.
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http://people.tcd.ie/millskhttp://people.tcd.ie/lynchma
http://people.tcd.ie/ldungan
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European Journal of Immunology44
10
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T cells, NK cells, Macrophage, IFN-γ, EAESubject (TCD):
Immunology, Inflammation & InfectionDOI:
http://dx.doi.org/10.1002/eji.201444612ISSN:
0014-2980Metadata
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