Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6.

Authors: Giralt, Mercedes  Ramos, Raquel  Quintana, Albert  Ferrer, Beatriz  Erta, Maria  Castro-Freire, Marco  Comes, Gemma  Sanz, Elisenda  Unzeta, Mercedes  PifarrĂ©, Paula  GarcĂ­a, Agustina  Campbell, Iain L  Hidalgo, Juan 
Citation: Giralt M, etal., Glia. 2013 Apr;61(4):587-600. doi: 10.1002/glia.22457. Epub 2013 Jan 16.
Pubmed: (View Article at PubMed) PMID:23322593
DOI: Full-text: DOI:10.1002/glia.22457

Interleukin (IL)-6 is crucial for the induction of many murine models of autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. While IL-6-deficient mice (IL-6 KO) are resistant to EAE, we showed previously that in transgenic mice with astrocyte-targeted production of IL-6-restricted to the cerebellum (GFAP-IL6), EAE induced with MOG(35-55) was redirected away from the spinal cord to the cerebellum. To further establish the importance of IL-6 produced in the central nervous system, we have generated mice producing IL-6 essentially only in the brain by crossing the GFAP-IL6 mice with IL-6 KO mice. Interestingly, GFAP-IL6-IL-6 KO mice showed a milder but almost identical phenotype as the GFAP-IL6 mice, which correlated with a lower load of inflammatory cells and decreased microglial reactivity. These results indicate that not only is cerebellar IL-6 production and eventual leakage into the peripheral compartment the dominating factor controlling this type of EAE but that it can also facilitate induction of autoimmunity in the absence of normal systemic IL-6 production.

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CRRD ID: 12791289
Created: 2017-03-06
Species: All species
Last Modified: 2017-03-06
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.