Type

Journal Article

Authors

Kingston Mills
Leonora Dungan
Marina Lynch

Subjects

Microbiology

Topics
macrophage autoimmune diseases immunology inflammation infection ifn myelin oligodendrocyte glycoprotein eae nk cells t cells

Innate IFN-gamma promotes development of experimental autoimmune encephalomyelitis: A role for NK cells and M1 macrophages. (2014)

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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Full list of authors on original publication

Kingston Mills, Leonora Dungan, Marina Lynch

Experts in our system

1
Kingston Mills
Trinity College Dublin
Total Publications: 182
 
2
Marina Annetta Lynch
Trinity College Dublin
Total Publications: 80