Mechanisms regulating regional localization of inflammation during CNS autoimmunity

Abstract

Summary Multiple sclerosis (MS) is a disease of the central nervous system (CNS) characterized by inflammatory, demyelinating lesions localized in the brain and spinal cord. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is induced by activating myelin-specific T cells and exhibits immune cell infiltrates in the CNS similar to those seen in MS. Both MS and EAE exhibit disease heterogeneity, reflecting variations in clinical course and localization of lesions within the CNS. Collectively, the differences seen in MS and EAE suggest that the brain and spinal cord function as unique microenvironments that respond differently to infiltrating immune cells. This review addresses the roles of the cytokines interferon-γ and interleukin-17 in determining the localization of inflammation to the brain or spinal cord in EAE.

12/15-lipoxygenase–mediated enzymatic lipid oxidation regulates DC maturation and function

“…Moreover, we observed increased levels of Il1b and an elevated expression of the Th17-specific transcription factor Rorgt in lymph nodes of Alox15 -/-mice. mediated autoimmune disease (17). After immunization with MOG peptide, newly primed autoreactive T cells invade the CNS, resulting in CNS inflammation and progressive paralysis.…”

Neutrophils Mediate Blood–Spinal Cord Barrier Disruption in Demyelinating Neuroinflammatory Diseases

“…PMNs are also increasingly recognized as having pivotal functions in driving inflammatory processes within the target organ, extending their role beyond that of bystander cells of the adaptive immune response (19)(20)(21). Recent findings present neutrophils as potent modulators of dendritic cell recruitment and function, which themselves are responsible for Ag presentation to encephalitogenic Th1 and Th17 cells following the latter's transmigration from the perivascular space into the parenchyma (22)(23)(24)(25)(26)(27). The activity of IFN-g-producing Th1 lymphocytes is suppressed by neutrophils in the CNS of EAE mice, and neutrophilderived myeloperoxidase was shown to inhibit dendritic cell activation, therefore dampening T cell-driven inflammation (28,29).…”

The Transcription Factor Twist1 Limits T Helper 17 and T Follicular Helper Cell Development by Repressing the Gene Encoding the Interleukin-6 Receptor α Chain

“…Th17 cells have been demonstrated to be crucial in mediating the development of EAE, the role of IFN-␥ and IL-17 in EAE disease has been controversial (40,41). Recently, GM-CSF, produced by Th1 and Th17 cells, has been identified as a contributor to the development of EAE (5, 42).…”