A new mouse model to study restoration of interleukin-6 (IL-6) expression in a Cre-dependent manner : microglial IL-6 regulation of experimental autoimmune encephalomyelitis
Sanchis, Paula (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Fernandez-Gayol, Olaya (Universitat Autònoma de Barcelona. Institut de Neurociències)
Comes, Gemma (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Aguilar Ludwig, Kevin (Universitat Autònoma de Barcelona. Institut de Neurociències)
Escrig, Anna (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Giralt, Mercedes (Universitat Autònoma de Barcelona. Institut de Neurociències)
Palmiter, Richard D. (University of Washington. Department of Biochemistry)
Hidalgo Pareja, Juan (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Data:	2020
Resum:	Interleukin-6 (IL-6) is a pleiotropic cytokine that controls numerous physiological processes both in basal and neuroinflammatory conditions, including the inflammatory response to experimental autoimmune encephalomyelitis (EAE). IL-6 is produced by multiple peripheral and central cells, and until now, the putative roles of IL-6 from different cell types have been evaluated through conditional cell-specific IL-6 knockout mice. Nevertheless, these mice probably undergo compensatory responses of IL-6 from other cells, which makes it difficult to assess the role of each source of IL-6. To give some insight into this problem, we have produced a novel mouse model: a conditional reversible IL-6 KO mouse (IL6-DIO-KO). By using double-inverted, open-reading-frame (DIO) technology, we created a mouse line with the loss of Il6 expression in all cells that can be restored by the action of Cre recombinase. Since microglia are one of the most important sources and targets of IL-6 into the central nervous system, we have recovered microglial Il6 expression in IL6-DIO-KO mice through breeding to Cx3cr1 -CreER mice and subsequent injection of tamoxifen (TAM) when mice were 10-16 weeks old. Then, they were immunized with myelin oligodendrocyte glycoprotein 35-55 peptide (MOG) 7 weeks after TAM treatment to induce EAE. Clinical symptoms and demyelination, CD3 infiltration, and gliosis in the spinal cord were evaluated. IL6-DIO-KO mice were resistant to EAE, validating the new model. Restoration of microglial Il6 was sufficient to develop a mild version of EAE-related clinical symptoms and neuropathology. IL6-DIO-KO mouse is an excellent model to understand in detail the role of specific cellular sources of IL-6 within a recovery-of-function paradigm in EAE.
Ajuts:	Ministerio de Economía y Competitividad BES-2015-071959 Ministerio de Educación, Cultura y Deporte FPU/2012-00365 Ministerio de Educación, Cultura y Deporte FPU17/02065 Ministerio de Economía y Competitividad SAF2014-56546-R Ministerio de Economía y Competitividad RTI2018-101105-B-I00
Nota:	Altres ajuts: "La Marató TV3" 20142210
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	DIO technology ; Conditional reversible IL-6 knockout ; Experimental autoimmune encephalomyelitis ; Microglial IL-6
Publicat a:	Journal of neuroinflammation, Vol. 17 (October 2020) , art. 304, ISSN 1742-2094

DOI: 10.1186/s12974-020-01969-0
PMID: 33059703

17 p, 6.0 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Neurociències (INc)
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