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

Immunology and Cell Biology - Tập 90 Số 5 - Trang 505-509 - 2012
Ulrich Kalinke1, Marco Prinz2,3
1Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz-Centre for Infection Research (HZI), Braunschweig, and the Hannover Medical School (MHH), Hannover, Germany
2BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany
3Department of Neuropathology, University of Freiburg, Freiburg, Germany

Tóm tắt

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.

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Thông tin xuất bản

Immunology and Cell Biology

Tập 90 Số 5

505-509

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