Suppression Of Experimental Autoimmune Encephalomyelitis Research Articles

Synergistic Targeting of Innate Receptors TLR7 and NOD2 for Therapeutic Intervention in Multiple Sclerosis

Regulation of neuroinflammation is critical for maintaining central nervous system (CNS) homeostasis and holds therapeutic promise in autoimmune diseases such as multiple sclerosis (MS). Previous studies have highlighted the significance of selective innate signaling in triggering anti-inflammatory mechanisms, which play a protective role in an MS-like disease, experimental autoimmune encephalomyelitis (EAE). However, the individual intra-CNS administration of specific innate receptor ligands or agonists, such as for toll-like receptor 7 (TLR7) and nucleotide-binding oligomerization-domain-containing protein 2 (NOD2), failed to elicit the desired anti-inflammatory response in EAE. In this study, we investigated the potential synergistic effect of targeting both TLR7 and NOD2 simultaneously to prevent EAE progression. Our findings demonstrate that simultaneous intrathecal administration of NOD2- and TLR7-agonists led to synergistic induction of Type I IFN (IFN I) and effectively suppressed EAE in an IFN I-dependent manner. Suppression of EAE was correlated with a significant decrease in the infiltration of monocytes, granulocytes, and natural killer cells, reduced demyelination, and downregulation of IL-1β, CCL2, and IFNγ gene expression in the spinal cord. These results underscore the therapeutic promise of concurrently targeting the TLR7 and NOD2 pathways in alleviating neuroinflammation associated with MS, paving the way for novel and more efficacious treatment strategies.

Synergistic Targeting of Innate Receptors TLR7 and NOD2 for Therapeutic Intervention in Multiple Sclerosis.

Regulation of neuroinflammation is critical for maintaining central nervous system (CNS) homeostasis and holds therapeutic promise in autoimmune diseases such as multiple sclerosis (MS). Previous studies have highlighted the significance of selective innate signaling in triggering anti-inflammatory mechanisms, which play a protective role in an MS-like disease, experimental autoimmune encephalomyelitis (EAE). However, the individual intra-CNS administration of specific innate receptor ligands or agonists, such as for toll-like receptor 7 (TLR7) and nucleotide-binding oligomerization-domain-containing protein 2 (NOD2), failed to elicit the desired anti-inflammatory response in EAE. In this study, we investigated the potential synergistic effect of targeting both TLR7 and NOD2 simultaneously to prevent EAE progression. Our findings demonstrate that simultaneous intrathecal administration of NOD2- and TLR7-agonists led to synergistic induction of Type I IFN (IFN I) and effectively suppressed EAE in an IFN I-dependent manner. Suppression of EAE was correlated with a significant decrease in the infiltration of monocytes, granulocytes, and natural killer cells, reduced demyelination, and downregulation of IL-1β, CCL2, and IFNγ gene expression in the spinal cord. These results underscore the therapeutic promise of concurrently targeting the TLR7 and NOD2 pathways in alleviating neuroinflammation associated with MS, paving the way for novel and more efficacious treatment strategies.

Suppression of Experimental Autoimmune Encephalomyelitis in Mice by β-Hydroxy β-Methylbutyrate, a Body-Building Supplement in Humans.

Although several immunomodulatory drugs are available for multiple sclerosis (MS), most present significant side effects with long-term use. Therefore, delineation of nontoxic drugs for MS is an important area of research. β-Hydroxy β-methylbutyrate (HMB) is accessible in local GNC stores as a muscle-building supplement in humans. This study underlines the importance of HMB in suppressing clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of MS. Dose-dependent study shows that oral HMB at a dose of 1 mg/kg body weight/d or higher significantly suppresses clinical symptoms of EAE in mice. Accordingly, orally administered HMB attenuated perivascular cuffing, preserved the integrity of the blood-brain barrier and blood-spinal cord barrier, inhibited inflammation, maintained the expression of myelin genes, and blocked demyelination in the spinal cord of EAE mice. From the immunomodulatory side, HMB protected regulatory T cells and suppressed Th1 and Th17 biasness. Using peroxisome proliferator-activated receptor (PPAR)α-/- and PPARβ-/- mice, we observed that HMB required PPARβ, but not PPARα, to exhibit immunomodulation and suppress EAE. Interestingly, HMB reduced the production of NO via PPARβ to protect regulatory T cells. These results describe a novel anti-autoimmune property of HMB that may be beneficial in the treatment of MS and other autoimmune disorders.

Targeting Signaling Pathway Downstream of RIG-I/MAVS in the CNS Stimulates Production of Endogenous Type I IFN and Suppresses EAE.

Type I interferons (IFN), including IFNβ, play a protective role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Type I IFNs are induced by the stimulation of innate signaling, including via cytoplasmic RIG-I-like receptors. In the present study, we investigated the potential effect of a chimeric protein containing the key domain of RIG-I signaling in the production of CNS endogenous IFNβ and asked whether this would exert a therapeutic effect against EAE. We intrathecally administered an adeno-associated virus vector (AAV) encoding a fusion protein comprising RIG-I 2CARD domains (C) and the first 200 amino acids of mitochondrial antiviral-signaling protein (MAVS) (M) (AAV-CM). In vivo imaging in IFNβ/luciferase reporter mice revealed that a single intrathecal injection of AAV-CM resulted in dose-dependent and sustained IFNβ expression within the CNS. IFNβ expression was significantly increased for 7 days. Immunofluorescent staining in IFNβ-YFP reporter mice revealed extraparenchymal CD45+ cells, choroid plexus, and astrocytes as sources of IFNβ. Moreover, intrathecal administration of AAV-CM at the onset of EAE induced the suppression of EAE, which was IFN-I-dependent. These findings suggest that accessing the signaling pathway downstream of RIG-I represents a promising therapeutic strategy for inflammatory CNS diseases, such as MS.

Suppression of experimental autoimmune encephalomyelitis by IgG Fc fragments bearing regRF epitopes

Previously we identified a rheumatoid factor, the production of which provides rats with resistance to experimental autoimmune diseases. It has been named regulatory rheumatoid factor (regRF). Immunization with conformers of IgG Fc fragments carrying epitopes specific to regRF reduces rat collagen-induced arthritis. The aim of this study was to determine whether IgG Fc fragments bearing regRF epitopes suppress experimental autoimmune encephalomyelitis, and to evaluate the potential of a strategy of stimulating production of regRF to treat multiple sclerosis. Two days after myelin basic protein injection, rats were immunized with Fc fragments exhibiting regRF epitopes, as well as with Fc fragments without those epitopes. The effect of Fc immunization on clinical signs of EAE and immunological parameters was evaluated. Stimulation of regRF production by IgG Fc fragments bearing regRF epitopes diminished EAE symptoms in rats, while immunization with Fc fragments without those epitopes worsened EAE. The improvement of EAE symptoms in rats treated with Fc fragments bearing regRF epitopes was associated with regRF production and with the relatively low number of blood CD4 T lymphocytes during disease development. In experiments involving immunizing intact rats and lymph node mononuclear cell cultures, Fc fragments bearing regRF epitopes decreased the CD4 T lymphocyte population indirectly, via regRF production. RegRF is a promising biotarget in MS, and Fc fragments bearing regRF epitopes are a potential therapeutic agent for MS.

Co-treatments to Boost IDO Activity and Inhibit Production of Downstream Catabolites Induce Durable Suppression of Experimental Autoimmune Encephalomyelitis.

Reinforcing defective tolerogenic processes slows progression of autoimmune (AI) diseases and has potential to promote drug-free disease remission. Previously, we reported that DNA nanoparticles (DNPs) and cyclic dinucleotides (CDNs) slow progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, by activating the Stimulator of Interferon Genes (STING) signaling adaptor to stimulate interferon type 1 (IFN-I) production, which induced dendritic cells to express indoleamine 2,3 dioxygenase (IDO) and acquire immune regulatory phenotypes. Here, we show that therapeutic responses to DNPs depend on DNA sensing via cyclic GAMP synthase (cGAS) and interactions between Programmed Death-1 (PD-1) and PD-1 ligands. To investigate how increased tryptophan (Trp) metabolism by IDO promotes therapeutic responses mice were co-treated at EAE onset with DNPs and drugs that inhibit kynurenine aminotransferase-II (KatII) or 3-hydroxyanthranilic acid dioxygenase (HAAO) activity downstream of IDO in the kynurenine (Kyn) pathway. DNP and KatII or HAAO inhibitor co-treatments suppressed EAE progression more effectively than DNPs, while KatII inhibition had no significant therapeutic benefit and HAAO inhibition attenuated but did not prevent EAE progression. Moreover, therapeutic responses to co-treatments were durable as EAE progression did not resume after co-treatment. Thus, using STING agonists to boost IDO activity and manipulating the Kyn pathway downstream of IDO is an effective strategy to enhance tolerogenic responses that overcome autoimmunity to suppress EAE progression.

CBD Suppression of EAE Is Correlated with Early Inhibition of Splenic IFN-γ + CD8+ T Cells and Modest Inhibition of Neuroinflammation.

In this study cannabidiol (CBD) was administered orally to determine its effects and mechanisms in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). We hypothesized that 75mg/kg of oral CBD given for 5days after initiation of disease would reduce EAE severity through suppression of either the early peripheral immune or late neuroimmune response. EAE was induced in C57BL/6 mice at two different magnitudes, and peripheral inflammatory and neuroinflammatory responses were measured at days 3, 10, and 18. Th1, Th17, Tc1, Tc17, Tregs, and myeloid derived suppressor cells (MDSC) were identified from the lymph nodes and spleens of each mouse to determine if CBD altered the suppressor cell or inflammatory cell populations in secondary lymphoid tissues. Additionally, neuroinflammation was identified in brain and spinal cord tissues using various immunohistochemical techniques and flow cytometry. Early treatment of EAE with oral CBD reduced clinical disease at the day 18 timepoint which correlated with a significant decrease in the percentage of MOG35-55 specific IFN-γ producing CD8+ T cells in the spleen at day 10. Analysis of both T cell infiltration and lesion size within the spinal cord also showed a moderate reduction in neuroinflammation within the central nervous system (CNS). These results provide evidence that oral CBD suppressed the peripheral immune response that precedes neuroinflammation; however, analysis of the neuroinflammatory endpoints also suggest that the modest reduction in neuroinflammation was only partially responsible for CBD's neuroprotective capability. Graphical Abstract CBD was administered orally for the first 5days following initiation of EAE. CBD attenuated clinical disease, and we found that CBD suppressed IFN-γ producing CD8+ T cells in the spleen at day 10. There was also modest suppression of neuroinflammation. Together these data demonstrate that early, oral administration of CBD protected mice from disease, but the modest effects on neuroinflammation suggest other mechanisms participate in CBD's neuroprotective effect in EAE.

Foxp3+ regulatory T cells play an indispensable role during glucocorticoid-induced treatment of autoimmune inflammation

Abstract Glucocorticoid (GC) is a class of steroid hormones with profound immunosuppressive and anti-inflammatory properties that is widely used as the first-line treatment option in chronic inflammatory conditions such as autoimmunity. Despite the broad usage, its working mechanisms remain largely unclear. Herein, we report that Foxp3+ CD4+ regulatory T cells (Tregs) play an irreplaceable role during GC-mediated treatment of experimental autoimmune encephalomyelitis (EAE), a murine autoimmune inflammation model in the central nervous system that resembles multiple sclerosis in human. Dexamethasone (Dex) administered at the disease onset or ongoing disease was unable to suppress EAE without Tregs, while adoptive transfer of Tregs restored Dex effects. Glucocorticoid receptor (GR) expression in Tregs was essential for Dex effects, suggesting that GC directly acts on Tregs. From RNA sequencing analysis we found that Dex treatment induced miR-342 expression only in Tregs but not in effector T cells. We also found that miR-342 targets the Rictor, a subunit of the mTORC2 complex. Inhibiting Dex-induced miR-342 expression in Tregs not only restored Rictor expression but also interfered with Treg-mediated suppression of EAE even with Dex treatment. While Dex-stimulated Tregs displayed robust oxidative phosphorylation rather than glycolysis as the energy source, miR-342 inhibition in Tregs reversed metabolic program to robust glycolysis. Taken together, this is the first report demonstrating that the miR-342-Rictor axis may represent a novel mechanism by which GC controls inflammation by metabolic programming in Tregs.

UV light suppression of EAE (a mouse model of multiple sclerosis) is independent of vitamin D and its receptor

Vitamin D and sunlight have each been reported to protect against the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). To date, the contribution of each has been unclear as ultra violet (UV) exposure also causes the generation of vitamin D in the skin. To examine whether the UV based suppression of EAE results, at least, in part from the production of vitamin D, we studied the effect of UV light on EAE in mice unable to produce 7-dehydroxycholesterol (7-DHC), the required precursor of vitamin D. Furthermore, we examined UV suppression of EAE in mice devoid of the vitamin D receptor (VDR). Our results demonstrate that UV light suppression of EAE occurs in the absence of vitamin D production and in the absence of VDR. Future investigations will focus on identifying the pathway responsible for the protective action of UV in EAE and presumably human MS.

Bee venom phospholipase A2 suppression of experimental autoimmune encephalomyelitis is dependent on its enzymatic activity

Backgrounds: Bee venom has been used as an alternative medicine for immune-related diseases such as multiple sclerosis (MS). Previously, we showed that Bee venom exerts a therapeutic effect in a mouse model of MS through regulatory T cells (Tregs) and Phospholipase A2 from bee venom (bvPLA2) induces a differentiation of Tregs. Methods: To induce EAE, C57BL/6 mice were injected MOG35-55 peptide in CFA and pertussis toxin. To ascertain whether Tregs were involved in the neural protective effect of bvPLA2, the mice received a PC61 an-ti-CD25 mAb to deplete Tregs or normal anti-rat IgG1 for an isotype control. To verify the necessity of enzymatic activity experimentally, we synthesized a recombinant bvPLA2 and mutant bvPLA2, which has no catalytic ability. Results: The limb paralysis caused by EAE was significantly attenuated in the bvPLA2-treated mice compared to the PBS-treated mice. The beneficial effects of bvPLA2 disappeared when Tregs were depleted. Synthetic bvPLA2 showed therapeutic effects such as those of the natural bvPLA2; however, the mutant which has no catalytic ability did not. Conclusion: Our findings suggest that bvPLA2 contributes to the control of MS and that its catalytic ability is needed for its therapeutic action.

The PD-1/PD-Ls pathway is up-regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides

Multiple sclerosis (MS) is an inflammatory demyelinating disease of CNS. Astragalus polysaccharides (APS), the main active extract from astragalus membranaceus which is a kind of traditional Chinese medicinal herb, is associated with a variety of immunomodulatory activities. We have evaluated the therapeutic effects of APS in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). It was found that APS could effectively alleviate EAE through inhibiting MOG35–55-specific T cell proliferation and reducing the expression of proinflammatory cytokines, which is mediated by up-regulating the expression of PD-1/PD-Ls signaling pathway. Our results demonstrated that EAE could be suppressed significantly by APS administration. It indicated that APS might be a potential of developing innovative drug for the therapy of MS.

Therapeutic efficacy of multipotent adult progenitor cells versus mesenchymal stem cells in experimental autoimmune encephalomyelitis.

In this study, we have evaluated the therapeutic efficacy of mouse multipotent adult progenitor cells (mMAPCs) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, and compared it with mouse mesenchymal stem cells (mMSCs). We administered PKH26-labeled mMAPC and mMSC into EAE mice and evaluated their therapeutic efficacy. The mMAPC-treated mice in comparison with the mMSC group exhibited a higher suppression of EAE (p < 0.05), and a higher fold expression of neuronal genes GAP43, NG2, PDGFR, Nestin, SMI 32, BDNF and NT 3 in spinal cord (p < 0.05), suggesting a better neuroprotective and regenerative potential of mMAPC than mMSC. MAPC may be a potential cell type, which is superior to mesenchymal stem cell for the treatment of EAE/multiple sclerosis.

Suppression of experimental autoimmune encephalomyelitis by ultraviolet light is not mediated by isomerization of urocanic acid

BackgroundUltraviolet B irradiation confers strong resistance against experimental autoimmune encephalomyelitis, a model of multiple sclerosis. This protection by ultraviolet B is independent of vitamin D production but causes isomerization of urocanic acid, a naturally occurring immunosuppressant.MethodsTo determine whether UCA isomerization from trans to cis is responsible for the protection against experimental autoimmune encephalomyelitis afforded by ultraviolet B, trans- or cis-urocanic acid was administered to animals and their disease progression was monitored.ResultsDisease incidence was reduced by 74% in animals exposed to ultraviolet B, and skin cis-urocanic acid levels increased greater than 30%. However, increasing skin cis-urocanic acid levels independent of ultraviolet B was unable to alter disease onset or progression.ConclusionsIt is unlikely that urocanic acid isomerization is responsible for the ultraviolet B-mediated suppression of experimental autoimmune encephalomyelitis. Additional work is needed to investigate alternative mechanisms by which UVB suppresses disease.

Selective depletion of CD11c+ CD11b+ dendritic cells partially abrogates tolerogenic effects of intravenous MOG in murine EAE.

Intravenous (i.v.) injection of a soluble myelin antigen can induce tolerance, which effectively ameliorates experimental autoimmune encephalomyelitis (EAE). We have previously shown that i.v. myelin oligodendrocyte glycoprotein (MOG) induces tolerance in EAE and expands a subpopulation of tolerogenic CD11c+ CD11b+ dendritic cells (DCs) with an immature phenotype having low expression of IA and co-stimulatory molecules CD40, CD86, and CD80. Here, we further investigate the role of tolerogenic DCs in i.v. tolerance by injecting clodronate-loaded liposomes, which selectively deplete CD11c+ CD11b+ and immature DCs, but not CD11c+ CD8+ DCs and mature DCs. I.v. MOG-induced suppression of EAE was partially, yet significantly, blocked by CD11c+ CD11b+ DC depletion. While i.v. MOG inhibited IA, CD40, CD80, CD86 expression and induced TGF-β, IL-27, IL-10 production in CD11c+ CD11b+ DCs, these effects were abrogated after injection of clodronate-loaded liposomes. Depletion of CD11c+ CD11b+ DCs also precluded i.v. autoantigen-induced T-cell tolerance, such as decreased production of IL-2, IFN-γ, IL-17 and numbers of IL-2+ , IFN-γ+ , and IL-17+ CD4+ T cells, as well as an increased proportion of CD4+ CD25+ Foxp3+ regulatory T cells and CD4+ IL-10+ Foxp3- Tr1 cells. CD11c+ CD11b+ DCs, through low expression of IA and costimulatory molecules as well as high expression of TGF-β, IL-27, and IL-10, play an important role in i.v. tolerance-induced EAE suppression.

The suppression of experimental autoimmune encephalomyelitis by intraperitoneal administration of HuangQi Glycoprotein

The suppression of experimental autoimmune encephalomyelitis by intraperitoneal administration of HuangQi Glycoprotein

The Active Form of Vitamin D Transcriptionally Represses Smad7 Signaling and Activates Extracellular Signal-regulated Kinase (ERK) to Inhibit the Differentiation of a Inflammatory T Helper Cell Subset and Suppress Experimental Autoimmune Encephalomyelitis

The ability of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), to transcriptionally modulate Smads to inhibit Th17 differentiation and experimental autoimmune encephalomyelitis (EAE) has not been adequately studied. This study reports modulation of Smad signaling by the specific binding of the VDR along with its heterodimeric partner RXR to the negative vitamin D response element on the promoter of Smad7, which leads to Smad7 gene repression. The vitamin D receptor-mediated increase in Smad3 expression partially explains the IL10 augmentation seen in Th17 cells. Furthermore, the VDR axis also modulates non-Smad signaling by activating ERK during differentiation of Th17 cells, which inhibits the Th17-specific genes il17a, il17f, il22, and il23r. In vivo EAE experiments revealed that, 1,25(OH)2D3 suppression of EAE correlates with the Smad7 expression in the spleen and lymph nodes. Furthermore, Smad7 expression also correlates well with IL17 and IFNγ expression in CNS infiltered inflammatory T cells. We also observed similar gene repression of Smad7 in in vitro differentiated Th1 cells when cultured in presence of 1,25(OH)2D3. The above canonical and non-canonical pathways in part address the ability of 1,25(OH)2D3-VDR to inhibit EAE.

UV light selectively inhibits spinal cord inflammation and demyelination in experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). The incidence of MS is inversely related to sun light exposure or ultraviolet radiation (UVR). UVR was found to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of MS, independent of vitamin D production. The mechanism of this suppression remains to be elucidated. To this end, several elements of an immune response in the spinal cord, spleen and skin during development of EAE were studied. As expected, UVR (10kJ/m2) inhibits inflammation and demyelination of the spinal cord. Most significant, UVR dramatically reduced spinal cord chemokine CCL5 mRNA and protein levels. UVR also suppressed IL-10 in skin and spleen but not the spinal cord. As expected from the UVR action on skin, macrophage population and IFN-γ levels are increased in that organ. UVR had no effect on lymphocyte proliferation and IFN-γ in spleen. From these measurements, we suggest that UVR suppression of EAE prevents the migration of inflammatory cells into the CNS by a focal inhibition of chemokine CCL-5 in the CNS and a systemic elevation of immunosuppressive IL-10.

Neuroantigen-specific autoregulatory CD8+ T cells inhibit autoimmune demyelination through modulation of dendritic cell function.

Experimental autoimmune encephalomyelitis (EAE) is a well-established murine model of multiple sclerosis, an immune-mediated demyelinating disorder of the central nervous system (CNS). We have previously shown that CNS-specific CD8+ T cells (CNS-CD8+) ameliorate EAE, at least in part through modulation of CNS-specific CD4+ T cell responses. In this study, we show that CNS-CD8+ also modulate the function of CD11c+ dendritic cells (DC), but not other APCs such as CD11b+ monocytes or B220+ B cells. DC from mice receiving either myelin oligodendrocyte glycoprotein-specific CD8+ (MOG-CD8+) or proteolipid protein-specific CD8+ (PLP-CD8+) T cells were rendered inefficient in priming T cell responses from naïve CD4+ T cells (OT-II) or supporting recall responses from CNS-specific CD4+ T cells. CNS-CD8+ did not alter DC subset distribution or MHC class II and CD86 expression, suggesting that DC maturation was not affected. However, the cytokine profile of DC from CNS-CD8+ recipients showed lower IL-12 and higher IL-10 production. These functions were not modulated in the absence of immunization with CD8-cognate antigen, suggesting an antigen-specific mechanism likely requiring CNS-CD8-DC interaction. Interestingly, blockade of IL-10 in vitro rescued CD4+ proliferation and in vivo expression of IL-10 was necessary for the suppression of EAE by MOG-CD8+. These studies demonstrate a complex interplay between CNS-specific CD8+ T cells, DC and pathogenic CD4+ T cells, with important implications for therapeutic interventions in this disease.

Suppression of experimental autoimmune encephalomyelitis by interleukin-10 transduced neural stem/progenitor cells

Neural stem/progenitor cells (NSPCs) have the ability to migrate into the central nervous system (CNS) to replace damaged cells. In inflammatory CNS disease, cytokine transduced neural stem cells may be used as vehicles to specifically reduce inflammation and promote cell replacement. In this study, we used NSPCs overexpressing IL-10, an immunomodulatory cytokine, in an animal model for CNS inflammation and multiple sclerosis (MS). Intravenous injection of IL-10 transduced neural stem/progenitor cells (NSPCIL-10) suppressed myelin oligodendrocyte glycoprotein aa 35–55 (MOG35-55)- induced experimental autoimmune encephalomyelitis (EAE) and, following intravenous injection, NSPCIL-10 migrated to peripheral lymphoid organs and into the CNS. NSPCIL-10 suppressed antigen-specific proliferation and proinflammatory cytokine production of lymph node cells obtained from MOG35-55 peptide immunized mice. In this model, IL-10 producing NSPCs act via a peripheral immunosuppressive effect to attenuate EAE.

Suppression of experimental autoimmune encephalomyelitis by 300–315 nm ultraviolet light

Multiple sclerosis (MS) is a chronic debilitating disease, with lowest incidence in equatorial regions and highest incidence in temperate regions. This relationship is believed to be related to sunlight or UV light exposure. Recent evidence with experimental autoimmune encephalomyelitis (EAE), an animal model of MS, established that this suppression is not mediated by vitamin D production. UV is comprised of three general wave bands: UVC (100–280nm), UVB (280–320nm) and UVA (320–400nm). In the present study we used four lamps that emit different wavelengths of UV: (1) broad band UVB (BB-UVB: 280–320nm); (2) narrow band UVB (NB-UVB: 300–315nm); (3) broad band UVA (BB-UVA: 300–400nm); and (4) long wavelength UVA (UVA-1: 340–400nm). The effect of these light sources was studied in vitamin D-sufficient C57BL/6 mice. The NB-UVB largely accounted for the suppression and delay of onset of EAE by BB-UVB. In contrast, UVA-1 failed to suppress EAE severity at low (∼2.5KJ/m2), medium (∼5.0KJ/m2) and high (∼10.0KJ/m2) doses. Serum calcium and 25-(OH)D3 levels were unchanged after both NB-UVB and UVA-1 treatments. The results demonstrate that NB-UVB (300–315nm) is largely responsible for light-induced suppression of EAE and its effect is not via production of vitamin D.