VPAC1 receptor (Vipr1)-deficient mice exhibit ameliorated experimental autoimmune encephalomyelitis, with specific deficits in the effector stage
In: ISSN: 1742-2094 ; Journal of Neuroinflammation ; https://www.hal.inserm.fr/inserm-01339481 ; Journal of Neuroinflammation, 2016, 2016
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International audience ; Background: Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating polypeptide (PACAP) are two highly homologous neuropeptides. In vitro and ex vivo experiments repeatedly demonstrate that these peptides exert pronounced immunomodulatory (primarily anti-inflammatory) actions which are mediated by common VPAC1 and VPAC2 G protein-coupled receptors. In agreement, we have shown that mice deficient in PACAP ligand or VPAC2 receptors exhibit exacerbated experimental autoimmune encephalomyelitis (EAE). However, we observed that VIP-deficient mice are unexpectedly resistant to EAE, suggesting a requirement for this peptide at some stage of disease development. Here, we investigated the involvement of VPAC1 in the development of EAE using a VPAC1-deficient mouse model.Methods: EAE was induced in wild-type (WT) and VPAC1 knockout (KO) mice using myelin oligodendrocyte glycoprotein 35–55 (MOG35–55), and clinical scores were assessed continuously over 30 days. Immune responses in the spinal cords were determined by histology, real-time PCR and immunofluorescence, and in the draining lymph nodes by antigen-recall assays. The contribution of VPAC1 expression in the immune system to the development of EAE was evaluated by means of adoptive transfer and bone marrow chimera experiments. In other experiments, VPAC1 receptor analogs were given to WT mice.Results: MOG35–55-induced EAE was ameliorated in VPAC1 KO mice compared to WT mice. The EAE-resistant phenotype of VPAC1 KO mice correlated with reduced central nervous system (CNS) histopathology and cytokine expression in the spinal cord. The immunization phase of EAE appeared to be unimpaired because lymph node cells from EAE-induced VPAC1 KO mice stimulated in vitro with MOG exhibited robust proliferative and Th1/Th17 responses. Moreover, lymph node and spleen cells from KO mice were fully capable of inducing EAE upon transfer to WT recipients. In contrast, WT cells from MOG-immunized mice did not transfer the disease when ...
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VPAC1 receptor (Vipr1)-deficient mice exhibit ameliorated experimental autoimmune encephalomyelitis, with specific deficits in the effector stage
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Autor/in / Beteiligte Person: | Abad, Catalina ; Jayaram, Bhavaani ; Becquet, Laurine ; Wang, Yuki ; O’dorisio, Sue ; Waschek, James ; Tan, Yossan-Var ; Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes ; Université de Rouen Normandie (UNIROUEN) ; Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Department of Psychiatry Los Angeles, USA ; University of California Los Angeles (UCLA) ; University of California (UC)-University of California (UC)-David Geffen School of Medicine Los Angeles ; University of California (UC)-University of California (UC) ; Department of Pediatrics and Holden Comprehensive Cancer Center Iowa City, USA ; University of Iowa Iowa City -Carver College of Medicine, University of Iowa ; This work was supported by the National Multiple Sclerosis Society RG4859,TA3048_A_1, RG-1501-02646, the National Institutes of Health (NIH)HD04612, and the ARSEP (Fondation pour l’aide à la recherche sur la scléroseen plaques). |
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Zeitschrift: | ISSN: 1742-2094 ; Journal of Neuroinflammation ; https://www.hal.inserm.fr/inserm-01339481 ; Journal of Neuroinflammation, 2016, 2016 |
Veröffentlichung: | HAL CCSD ; BioMed Central, 2016 |
Medientyp: | academicJournal |
DOI: | 10.1186/s12974-016-0626-3 |
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