scholarly journals Role of SOCS2 in the Regulation of Immune Response and Development of the Experimental Autoimmune Encephalomyelitis

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Allysson Cramer ◽  
Bruno Cabral de Lima Oliveira ◽  
Paulo Gaio Leite ◽  
David Henrique Rodrigues ◽  
Fatima Brant ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Immune Response ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Acute Phase ◽  
Critical Role ◽  
Recovery Phase ◽  
Cytokine Signaling ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Experimental Autoimmune Encephalomyelitis (EAE) is the most widely used animal model for the study of MS. The Suppressor of Cytokine Signaling (SOCS) 2 protein plays a critical role in regulating the immune responses. The role of SOCS2 during EAE has not been explored. EAE was induced in WT and SOCS2-/- mice using myelin oligodendrocyte glycoprotein (MOG35-55) peptide. Brain and spinal cord were examined during the peak (day 14) and recovery phase (day 28) of the disease. SOCS2 was upregulated in the brain of WT mice at the peak and recovery phase of EAE. The development of the acute phase was slower in onset in SOCS2-/- mice and was associated with reduced number of Th1 (CD3+CD4+IFN-γ+) cells in the spinal cord and brain. However, while in WT mice, maximal clinical EAE score was followed by a progressive recovery; the SOCS2-/- mice were unable to recover from locomotor impairment that occurred during the acute phase. There was a prolonged inflammatory response (increased Th1 and decreased Th2 and T regulatory cells) in the late phase of EAE in the CNS of SOCS2-/- mice. Transplantation of bone marrow cells from SOCS2-/- into irradiated WT mice resulted in higher lethality at the early phase of EAE. Altogether, these results suggest that SOCS2 plays a dual role in the immune response during EAE. It is necessary for damage during the acute phase damage but plays a beneficial role in the recovery stage of the disease.

scholarly journals Treatment With CD52 Antibody Protects Neurons in Experimental Autoimmune Encephalomyelitis Mice During the Recovering Phase

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenlin Hao ◽  
Qinghua Luo ◽  
Michael D. Menger ◽  
Klaus Fassbender ◽  
Yang Liu
Keyword(s):  
Spinal Cord ◽  
T Lymphocytes ◽  
Experimental Autoimmune Encephalomyelitis ◽  
B Lymphocytes ◽  
Neuroprotective Effect ◽  
Recovery Phase ◽  
Conditional Knockout ◽  
Autoimmune Encephalomyelitis ◽  
Inflammatory Infiltration ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic autoimmune disease driven by T and B lymphocytes. The remyelination failure and neurodegeneration results in permanent clinical disability in MS patients. A desirable therapy should not only modulate the immune system, but also promote neuroprotection and remyelination. To investigate the neuroprotective effect of CD52 antibody in MS, both C57BL/6J and SJL mice with experimental autoimmune encephalomyelitis (EAE) were treated with CD52 antibody at the peak of disease. Treatment with CD52 antibody depleted T but not B lymphocytes in the blood, reduced the infiltration of T lymphocytes and microglia/macrophages in the spinal cord. Anti-CD52 therapy attenuated EAE scores during the recovery phase. It protected neurons immediately after treatment (within 4 days) as shown by reducing the accumulation of amyloid precursor proteins. It potentially promoted remyelination as it increased the number of olig2/CC-1-positive mature oligodendrocytes and prevented myelin loss in the following days (e.g., 14 days post treatment). In further experiments, EAE mice with a conditional knockout of BDNF in neurons were administered with CD52 antibodies. Neuronal deficiency of BDNF attenuated the effect of anti-CD52 treatment on reducing EAE scores and inflammatory infiltration but did not affect anti-CD52 treatment-induced improvement of myelin coverage in the spinal cord. In summary, anti-CD52 therapy depletes CD4-positive T lymphocytes, prevents myelin loss and protects neurons in EAE mice. Neuronal BDNF regulates neuroprotective and anti-inflammatory effect of CD52 antibody in EAE mice.

scholarly journals BCG and BCG/DNAhsp65 Vaccinations Promote Protective Effects without Deleterious Consequences for Experimental Autoimmune Encephalomyelitis

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sofia Fernanda Gonçalves Zorzella-Pezavento ◽  
Clara Pires Fujiara Guerino ◽  
Fernanda Chiuso-Minicucci ◽  
Thais Graziela Donegá França ◽  
Larissa Lumi Watanabe Ishikawa ◽  
...  
Keyword(s):  
Immune Response ◽  
Weight Loss ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Molecular Mimicry ◽  
Clinical Score ◽  
Recovery Phase ◽  
Protective Effects ◽  
Autoimmune Encephalomyelitis ◽  
Inflammatory Infiltration ◽  
Experimental Autoimmune

A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65) after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE) development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γlevels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution.

scholarly journals Eosinophils are dispensable for development of MOG35-55-induced experimental autoimmune encephalomyelitis in mice

2021 ◽  
Author(s):  
Klara Ruppova ◽  
Jong-Hyung Lim ◽  
Georgia Fodelianaki ◽  
Avery August ◽  
Ales Neuwirth
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Potential Role ◽  
Autoimmune Encephalomyelitis ◽  
Eosinophil Granulocytes ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Deficient Mice ◽  
Experimental Autoimmune

AbstractExperimental autoimmune encephalomyelitis (EAE) represents the mouse model of multiple sclerosis, a devastating neurological disorder. EAE development and progression involves the infiltration of different immune cells into the brain and spinal cord. However, less is known about a potential role of eosinophil granulocytes for EAE disease pathogenesis. In the present study, we found enhanced eosinophil abundance accompanied by increased concentration of the eosinophil chemoattractant eotaxin-1 in the spinal cord in the course of EAE induced in C57BL/6 mice by immunization with MOG35-55 peptide. However, the absence of eosinophils did not affect neuroinflammation, demyelination and clinical development or severity of EAE, as assessed in ΔdblGATA1 eosinophil-deficient mice. Taken together, despite their enhanced abundance in the inflamed spinal cord during disease progression, eosinophils were dispensable for EAE development.

scholarly journals Deficiency of LRRC4 Accelerates Experimental Autoimmune Encephalomyelitis by Disrupting Th1/Treg Cell Balance

2019 ◽  
Author(s):  
Yan Zhang ◽  
Di Li ◽  
Qiuming Zeng ◽  
Jianbo Feng ◽  
Haijuan Fu ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Clinical Symptoms ◽  
Critical Role ◽  
Ectopic Expression ◽  
Treg Cells ◽  
Autism Spectrum ◽  
Th1 Cells ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Abstract Background Leucine rich repeat containing 4 (LRRC4), also known as netrin-G ligand-2 (NGL-2), belongs to the superfamily of LRR proteins and serves as a receptor for netrin-G2. LRRC4 regulates the formation of excitatory synapses and promotes axon differentiation. Mutations in LRRC4 occur in Autism Spectrum Disorder (ASD) and intellectual disability. Multiple sclerosis (MS) is a chronic autoimmune disease characterized by immune-mediated demyelination and neurodegeneration of the central nervous system (CNS). Here, we investigated the role of LRRC4 in the pathological process of experimental autoimmune encephalomyelitis (EAE), a widely used mouse model of MS.Methods LRRC4 was detected in the CNS of EAE mice by the use of real-time PCR and western blotting. LRRC4 -/- mice were created and immunized with myelin oligodendrocyte glycoprotein peptide (MOG) 35–55 . Pathological changes in spinal cords of LRRC4 -/- and WT mice 15 days after immunization were examined by using hematoxylin and eosin (H&E), Luxol Fast Blue (LFB) staining and immunohistochemistry. The number of Th1/Th2/Th17/Treg cells in spleens and blood were measured with flow cytometry. Differential gene expression in the spinal cords from WT and LRRC4 -/- mice was analyzed by using RNA sequencing (RNA-seq). Adeno-associated virus (AAV) vectors were used to overexpress LRRC4 (AAV-LRRC4) and were injected into EAE mice to assess the therapeutic effect of AAV-LRRC4 ectopic expression on EAE.Results We discovered that the level of LRRC4 decreases in the spinal cords of the EAE mice. Deletion of LRRC4 accelerates infiltration of leukocytes into the spinal cords and disease exacerbation in vivo. We further showed that LRRC4 deletion disrupts the balance between Th1 cells and Treg cells and causes a shift toward Th1 cells and that the disrupted balance may be attributed to up-regulation of IL-6, IFN-γ and down-regulation of TNF-α in EAE mice. At a mechanistic level, we found that deficiency of LRRC4 induces elevated NF-κB p65 expression and does so by up-regulating Rab7b, while ectopic expression of LRRC4 alleviates the clinical symptoms of EAE mice and protects the CNS from immune damages.Conclusions We establish a critical role of LRRC4 in the progression of EAE and provide novel mechanistic insights into EAE development. Our findings also suggest that LRRC4 may be used as a potential target for therapeutic treatment of MS.

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