Innate Interferons Regulate CNS Inflammation

Bidragets oversatte titel: Innate interferoner regulerer CNS inflammation

Ruthe Dieu, Reza M. H. Khorooshi, Anne Mariboe, Marie-Louise Hyre Arpe, Trevor Owens

Publikation: Konferencebidrag uden forlag/tidsskriftPosterFormidling


Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) whose pathology is characterised by demyelination and axonal damage. This results from interplay between CNS-resident glia, infiltrating leukocytes and a plethora of cytokines and chemokines. Currently, there is no cure for MS, however a standard first-line therapy is recombinant interferon (IFN)-beta. IFN-beta belongs to the family of type I IFNs, which also include IFN-alpha. These engage to one common receptor, IFNAR. Type I IFNs can be induced by several innate immune receptors, including toll-like receptors (TLRs), through signalling cascades involving either interferon regulatory factors (IRFs) or nuclear factor-kappa B (NF-kB). Several studies have identified a protective effect of type I IFNs in relation to experimental autoimmune encephalomyelitis (EAE), an MS-like disease in mice. Mice that lack IFN-beta or have disrupted IFNAR-signaling develop more severe disease, whereas peripheral IFN-beta treatment reduced disease severity and delayed onset. Furthermore, it was recently shown that induction of type I IFNs in the CNS of mice by a TLR3-ligand was protective against EAE. We are now investigating another potential IFN-inducing receptor that signals through NF-kB. Receptor activator of NF-kB (RANK) belongs to the TNF-receptor superfamily and has been shown to induce IFN-beta in medullary thymic epithelial cells affecting autoimmune regulatory processes and osteoclast precursor cells in association to bone mass homeostasis. Whether RANK-signaling is capable of inducing type I IFNs within the CNS has not yet been studied. Preliminary data from IFN-beta-luciferase reporter mice already show that RANK-signaling by intrathecally applied RANKL can induce CNS-endogenous IFN-beta. Experiments in IFN-beta-yellow fluorescence protein reporter mice identify extraparenchymal cells as one source of this IFN-beta and these will be identified using immunostaining and bone marrow chimera approaches. Studies are underway to examine whether IFN-alpha is also induced and the effect of RANK-induced IFN on EAE. The findings from this study will increase understanding of normal CNS homeostasis as well as identify new targets for MS therapy.
Bidragets oversatte titelInnate interferoner regulerer CNS inflammation
Publikationsdato29. sep. 2016
StatusUdgivet - 29. sep. 2016
Begivenhed13th International Congress of Neuroimmunology - Jerusalem, Israel
Varighed: 26. sep. 201629. sep. 2016
Konferencens nummer: 13


Konference13th International Congress of Neuroimmunology


  • Neuroimmunology