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

Mercedes Giralt, Raquel Ramos, Albert Quintana, Beatriz Ferrer, Maria Erta, Marco Castro-Freire, Gemma Comes, Elisenda Sanz, Mercedes Unzeta, Paula Pifarré, Agustina García, Iain L. Campbell, Juan Hidalgo

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 MOG35-55 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.

Original languageEnglish (US)
Pages (from-to)587-600
Number of pages14
JournalGlia
Volume61
Issue number4
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

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Autoimmune Experimental Encephalomyelitis
Astrocytes
Interleukin-6
Autoimmunity
Cerebellum
Transgenic Mice
Multiple Sclerosis
Spinal Cord
Central Nervous System
Animal Models
Phenotype

Keywords

  • Astrocyte
  • Autoimmunity
  • Microglia
  • T cells

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Giralt, M., Ramos, R., Quintana, A., Ferrer, B., Erta, M., Castro-Freire, M., ... Hidalgo, J. (2013). Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6. Glia, 61(4), 587-600. https://doi.org/10.1002/glia.22457

Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6. / Giralt, Mercedes; Ramos, Raquel; Quintana, Albert; Ferrer, Beatriz; Erta, Maria; Castro-Freire, Marco; Comes, Gemma; Sanz, Elisenda; Unzeta, Mercedes; Pifarré, Paula; García, Agustina; Campbell, Iain L.; Hidalgo, Juan.

In: Glia, Vol. 61, No. 4, 01.04.2013, p. 587-600.

Research output: Contribution to journalArticle

Giralt, M, Ramos, R, Quintana, A, Ferrer, B, Erta, M, Castro-Freire, M, Comes, G, Sanz, E, Unzeta, M, Pifarré, P, García, A, Campbell, IL & Hidalgo, J 2013, 'Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6', Glia, vol. 61, no. 4, pp. 587-600. https://doi.org/10.1002/glia.22457
Giralt, Mercedes ; Ramos, Raquel ; Quintana, Albert ; Ferrer, Beatriz ; Erta, Maria ; Castro-Freire, Marco ; Comes, Gemma ; Sanz, Elisenda ; Unzeta, Mercedes ; Pifarré, Paula ; García, Agustina ; Campbell, Iain L. ; Hidalgo, Juan. / Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6. In: Glia. 2013 ; Vol. 61, No. 4. pp. 587-600.
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