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IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8.
Sánchez-Fernández, Alba; Zandee, Stephanie; Amo-Aparicio, Jesús; Charabati, Marc; Prat, Alexandre; Garlanda, Cecilia; Eisenmesser, Elan Z; Dinarello, Charles A; López-Vales, Rubèn.
Afiliación
  • Sánchez-Fernández A; Institut de Neurociencies and Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, Bellaterra, Catalonia, Spain.
  • Zandee S; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED).
  • Amo-Aparicio J; Department of Neuroscience, Faculty of Medicine, Université de Montréal, and Neuroimmunology Unit, Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.
  • Charabati M; Institut de Neurociencies and Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, Bellaterra, Catalonia, Spain.
  • Prat A; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED).
  • Garlanda C; Department of Neuroscience, Faculty of Medicine, Université de Montréal, and Neuroimmunology Unit, Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.
  • Eisenmesser EZ; Department of Neuroscience, Faculty of Medicine, Université de Montréal, and Neuroimmunology Unit, Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.
  • Dinarello CA; Humanitas Clinical and Research Center, 20089 Rozzano, Italy.
  • López-Vales R; Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO 80238, USA.
Theranostics ; 11(1): 1-13, 2021.
Article en En | MEDLINE | ID: mdl-33391457
ABSTRACT

Background:

Interleukin 37 (IL-37), a member of IL-1 family, broadly suppresses inflammation in many pathological conditions by acting as a dual-function cytokine in that IL-37 signals via the extracellular receptor complex IL1-R5/IL-1R8, but it can also translocate to the nucleus. However, whether IL-37 exerts beneficial actions in neuroinflammatory diseases, such as multiple sclerosis, remains to be elucidated. Thus, the goals of the present study were to evaluate the therapeutic effects of IL-37 in a mouse model of multiple sclerosis, and if so, whether this is mediated via the extracellular receptor complex IL-1R5/IL-1R8.

Methods:

We used a murine model of MS, the experimental autoimmune encephalomyelitis (EAE). We induced EAE in three different single and double transgenic mice (hIL-37tg, IL-1R8 KO, hIL-37tg-IL-1R8 KO) and wild type littermates. We also induced EAE in C57Bl/6 mice and treated them with various forms of recombinant human IL-37 protein. Functional and histological techniques were used to assess locomotor deficits and demyelination. Luminex and flow cytometry analysis were done to assess the protein levels of pro-inflammatory cytokines and different immune cell populations, respectively. qPCRs were done to assess the expression of IL-37, IL-1R5 and IL-1R8 in the spinal cord of EAE, and in blood peripheral mononuclear cells and brain tissue samples of MS patients.

Results:

We demonstrate that IL-37 reduces inflammation and protects against neurological deficits and myelin loss in EAE mice by acting via IL1-R5/IL1-R8. We also reveal that administration of recombinant human IL-37 exerts therapeutic actions in EAE mice. We finally show that IL-37 transcripts are not up-regulated in peripheral blood mononuclear cells and in brain lesions of MS patients, despite the IL-1R5/IL-1R8 receptor complex is expressed.

Conclusions:

This study presents novel data indicating that IL-37 exerts therapeutic effects in EAE by acting through the extracellular receptor complex IL-1R5/IL-1R8, and that this protective physiological mechanism is defective in MS individuals. IL-37 may therefore represent a novel therapeutic avenue for the treatment of MS with great promising potential.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Médula Espinal / Encéfalo / Interleucina-1 / Receptores de Interleucina-1 / Esclerosis Múltiple Crónica Progresiva / Esclerosis Múltiple Recurrente-Remitente / Encefalomielitis Autoinmune Experimental Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Theranostics Año: 2021 Tipo del documento: Article País de afiliación: España

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Médula Espinal / Encéfalo / Interleucina-1 / Receptores de Interleucina-1 / Esclerosis Múltiple Crónica Progresiva / Esclerosis Múltiple Recurrente-Remitente / Encefalomielitis Autoinmune Experimental Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Theranostics Año: 2021 Tipo del documento: Article País de afiliación: España