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Neuropathology in multiple sclerosis is closely linked to presence of macrophages in the CNS. Both M1 (inflammatory) and M2 (alternatively activated, noninflammatory) macrophages are found in the inflamed CNS and thought to differentiate from infiltrating monocytes. It is unclear whether the balance of M1 and M2 macrophages can be altered and whether this affects disease outcome. We show in this article that Ly6C(hi) inflammatory monocytes are the early and dominant infiltrating cells in the CNS during experimental autoimmune encephalomyelitis, a model for the acute phase of multiple sclerosis. Activation of invariant NKT (iNKT) cells reduced the frequency of Ly6C(hi) monocytes and increased the proportion of M2 macrophages in the CNS with associated improvement in neurologic impairment. In contrast, iNKT-deficient mice showed higher numbers of Ly6C(hi) monocytes, reduced M2, and much more severe disease. Adoptive transfer of M2-enriched cells to iNKT-deficient mice markedly improved neurologic impairment. In vitro and in vivo experiments showed that iNKT cells promote differentiation of monocytes to M2 macrophages in an IL-4 and CD1d-dependent process. These findings indicate that infiltrating Ly6C(hi) inflammatory monocytes are early players in acute neuroinflammation and that their frequency and differentiation can be influenced by activation of iNKT cells with resultant improvement in disease outcome.

Original publication

DOI

10.4049/jimmunol.1103608

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

07/2012

Volume

189

Pages

551 - 557

Addresses

Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, UK.

Keywords

Monocytes, Cells, Cultured, Macrophages, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Encephalomyelitis, Autoimmune, Experimental, Acute Disease, Inflammation Mediators, Antigens, Ly, Lymphocyte Activation, Cell Differentiation, Cell Movement, Amino Acid Sequence, Female, Natural Killer T-Cells, Biomarkers