Suppression of Murine Experimental Autoimmune Optic Neuritis by Mature Dendritic Cells Transfected with Calcitonin Gene-Related Peptide Gene

Abstract

PURPOSE. Calcitonin gene-related peptide (CGRP) exhibits prominent anti-inflammatory actions. We examined whether CGRP-transfected dendritic cells (DC) prevent the development of experimental autoimmune optic neuritis (EAON) and experimental autoimmune encephalomyelitis (EAE). METHODS.A human CGRP-expressing plasmid was constructed, and used to transfect C57BL/6 mouse bone marrow-derived matured DC (mDC) by electroporation methods. Transfection efficiency was 50% with 80% cell viability. C57BL/6 mice were immunized with myelo-oligodendrocyte glycoprotein 35-55, and injected intravenously with CGRP-expressing mDC (CGRP gene-transfected group) or mock-transfected mDC (mocktransfected group) at the induction or effector phase. EAE was diagnosed clinically and EAON was assessed histopathologically. Delayed hypersensitivity was measured. Supernatants of spleen cell cultures were assayed for cytokines using ELISA.þ fraction in spleen cells was analyzed using flow cytometry.RESULTS. For gene therapy in the induction phase, EAE developed in 50% of mice in the CGRP-transfected group compared with 80% in the mock-transfected group, and the mean pathological score for EAON was 1 in the CGRPtransfected group compared with 2 in the mock-transfected group (P < 0.05). For gene therapy in the effector phase, the mean EAE clinical score (1.5 vs. 3.0) and mean EAON pathological score (1.0 vs. 2.0) were both lower in the CGRP-transfected group compared with the mock-transfected group (P < 0.05). Delayed hypersensitivity was suppressed significantly in the CGRP-transfected group. IL-10 production by spleen cells in the CGRP-transfected group increased independent of MOG concentration, compared with the mock-transfected group. Interestingly, the proportion ofþ cells increased significantly (P < 0.05) in the CGRP-transfected group compared with the mock-transfected group.CONCLUSIONS. Gene therapy with CGRP-expressing mDC was effective in suppressing the development of EAON and EAE. (Invest Ophthalmol Vis Sci. 2012;53:5475-5485)

The Experimental Autoimmune Encephalomyelitis Disease Course Is Modulated by Nicotine and Other Cigarette Smoke Components

“…There was no difference between these two groups (Figure S1). This result is in agreement with results described in the literature [25]. Depending on experimental design, the pumps were implanted either immediately after, 14 days after, or 14 days before the first injection of MOG.…”

Involvement of calcitonin gene-related peptide and receptor component protein in experimental autoimmune encephalomyelitis

“…Very recently, Matsuda et al (2012) showed that i.v. injection of dendritic cells transfected with CGRP reduced EAE development.…”

Calcitonin gene-related peptide is a key neurotransmitter in the neuro-immune axis

“…This has since been corroborated in models of psoriasis where TH17 cells are the dominant inflammatory phenotype (Ostrowski et al, 2011). In contrast, the association of CGRP with CD4+CD25+Foxp3+ cells has also been studied in a model of EAE (Matsuda et al, 2012). CGRP transfected DCs were able to increase differentiation of CD4+CD25+Foxp3+ regulatory cells (Matsuda et al, 2012).…”

“…In contrast, the association of CGRP with CD4+CD25+Foxp3+ cells has also been studied in a model of EAE (Matsuda et al, 2012). CGRP transfected DCs were able to increase differentiation of CD4+CD25+Foxp3+ regulatory cells (Matsuda et al, 2012). CGRP, is also produced by B lymphocytes in inflammatory conditions under the influence of nerve growth factor (NGF) (Bracci-Laudiero et al, 2002).…”