Activation of Invariant NKT Cells in Early Phase of Experimental Autoimmune Encephalomyelitis Results in Differentiation of Ly6Chi Inflammatory Monocyte to M2 Macrophages and Improved Outcome

Citations Over TimeTop 10% of 2012 papers

Abstract

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.

Related Papers

• → Activation of hepatic NKT cells and subsequent liver injury following administration of α-galactosylceramide(2000)254 cited
• → Targeted disruption of CD1d prevents NKT cell development in pigs(2015)23 cited
• → Role of NKT Cells in the Digestive System. II. NKT cells and diabetes(2007)8 cited
• → The Regulation of CD1d+ and CD1d− Tumors by NKT Cells(2011)1 cited
• → Discovery of a novel regulator of neuroinflammation: differential roles of SNS-1 in experimental autoimmune encephalomyelitis and lipopolysaccharide-induced neuroinflammation(2018)