Endogenous, or therapeutically induced, type I interferon responses differentially modulate Th1/Th17-mediated autoimmunity in the CNS.

2.50
Hdl Handle:
http://hdl.handle.net/10033/248820
Title:
Endogenous, or therapeutically induced, type I interferon responses differentially modulate Th1/Th17-mediated autoimmunity in the CNS.
Authors:
Kalinke, Ulrich; Prinz, Marco
Abstract:
Different viruses trigger pattern recognition receptor systems, such as Toll-like receptors or cytosolic RIG-I like helicases (RLH), and thus induce early type I interferon (IFN-I) responses. Such responses may confer protection until adaptive immunity is activated to an extent that the pathogen can be eradicated. Interestingly, the same innate immune mechanisms that are relevant for early pathogen defense have a role in ameliorating experimental autoimmune encephalomyelitis (EAE), a rodent model of human multiple sclerosis. We and others found that mice devoid of a component of the IFN-I receptor (Ifnar1(-/-)) showed significantly enhanced autoimmune disease of the central nervous system (CNS). A detailed analysis revealed that in wild-type mice IFN-I triggering of myeloid cells was instrumental in reducing brain damage. A more recent study indicated that similar to Ifnar1(-/-) mice, RLH-signaling-deficient mice showed enhanced autoimmune disease of the CNS as well. Moreover, when peripherally treated with synthetic RLH ligands wild-type animals with EAE disease showed reduced clinical scores. Under such conditions, IFN-I receptor triggering of dendritic cells had a crucial role. The therapeutic effect of treatment with RLH ligands was associated with negative regulation of Th1 and Th17 T-cell responses within the CNS. These experiments are consistent with the hypothesis that spatiotemporal conditions of, and cell types involved in, disease-ameliorating IFN-I responses differ significantly, depending on whether they were endogenously induced in the context of EAE pathogenesis within the CNS or upon therapeutic RLH triggering in the periphery. It is attractive to speculate that RLH triggering represents a new strategy to treat multiple sclerosis by stimulating endogenous immunoregulatory IFN-I responses.
Affiliation:
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz-Centre for Infection Research, Braunschweig, and the Hannover Medical School, MHH, Hannover, Germany. ulrich.kalinke@twincore.de
Citation:
Endogenous, or therapeutically induced, type I interferon responses differentially modulate Th1/Th17-mediated autoimmunity in the CNS. 2012, 90 (5):505-9 Immunol. Cell Biol.
Journal:
Immunology and cell biology
Issue Date:
May-2012
URI:
http://hdl.handle.net/10033/248820
DOI:
10.1038/icb.2012.8
PubMed ID:
22430251
Type:
Article
Language:
en
ISSN:
1440-1711
Appears in Collections:
Publications of the TwinCore unit experimental Infectionresearch(EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorKalinke, Ulrichen_GB
dc.contributor.authorPrinz, Marcoen_GB
dc.date.accessioned2012-10-15T14:09:06Z-
dc.date.available2012-10-15T14:09:06Z-
dc.date.issued2012-05-
dc.identifier.citationEndogenous, or therapeutically induced, type I interferon responses differentially modulate Th1/Th17-mediated autoimmunity in the CNS. 2012, 90 (5):505-9 Immunol. Cell Biol.en_GB
dc.identifier.issn1440-1711-
dc.identifier.pmid22430251-
dc.identifier.doi10.1038/icb.2012.8-
dc.identifier.urihttp://hdl.handle.net/10033/248820-
dc.description.abstractDifferent viruses trigger pattern recognition receptor systems, such as Toll-like receptors or cytosolic RIG-I like helicases (RLH), and thus induce early type I interferon (IFN-I) responses. Such responses may confer protection until adaptive immunity is activated to an extent that the pathogen can be eradicated. Interestingly, the same innate immune mechanisms that are relevant for early pathogen defense have a role in ameliorating experimental autoimmune encephalomyelitis (EAE), a rodent model of human multiple sclerosis. We and others found that mice devoid of a component of the IFN-I receptor (Ifnar1(-/-)) showed significantly enhanced autoimmune disease of the central nervous system (CNS). A detailed analysis revealed that in wild-type mice IFN-I triggering of myeloid cells was instrumental in reducing brain damage. A more recent study indicated that similar to Ifnar1(-/-) mice, RLH-signaling-deficient mice showed enhanced autoimmune disease of the CNS as well. Moreover, when peripherally treated with synthetic RLH ligands wild-type animals with EAE disease showed reduced clinical scores. Under such conditions, IFN-I receptor triggering of dendritic cells had a crucial role. The therapeutic effect of treatment with RLH ligands was associated with negative regulation of Th1 and Th17 T-cell responses within the CNS. These experiments are consistent with the hypothesis that spatiotemporal conditions of, and cell types involved in, disease-ameliorating IFN-I responses differ significantly, depending on whether they were endogenously induced in the context of EAE pathogenesis within the CNS or upon therapeutic RLH triggering in the periphery. It is attractive to speculate that RLH triggering represents a new strategy to treat multiple sclerosis by stimulating endogenous immunoregulatory IFN-I responses.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Immunology and cell biologyen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshDemyelinating Autoimmune Diseases, CNSen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunomodulationen_GB
dc.subject.meshImmunotherapyen_GB
dc.subject.meshInterferon Type Ien_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Knockouten_GB
dc.subject.meshMyeloid Cellsen_GB
dc.subject.meshReceptor, Interferon alpha-betaen_GB
dc.subject.meshTh1-Th2 Balanceen_GB
dc.subject.meshTh17 Cellsen_GB
dc.titleEndogenous, or therapeutically induced, type I interferon responses differentially modulate Th1/Th17-mediated autoimmunity in the CNS.en
dc.typeArticleen
dc.contributor.departmentInstitute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz-Centre for Infection Research, Braunschweig, and the Hannover Medical School, MHH, Hannover, Germany. ulrich.kalinke@twincore.deen_GB
dc.identifier.journalImmunology and cell biologyen_GB

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