Novel animal model of multiple sclerosis: The glial connexin gap junction as an environmental tuner for neuroinflammation

AbstractConnexins, which comprise gap junctions (GJs) via homotypic/heterotypic oligomerization, act as channels to connect opposing cells, mainly in solid organs such as the skin, liver, heart, and central/peripheral nervous system. Connexins are synthesized in the endoplasmic reticulum, assembled in the Golgi apparatus as hexamers, and inserted into the cell membrane as hemichannels. These hemichannels are closed under normal conditions until they combine to form clusters and connect to neighboring cells via GJs in a head ‐to‐head configuration. Opening of hemichannels, which depends on the intra‐ or extracellular environment, allows various bioactive molecules to enter into or be released from the host cells. Recent pathological studies on human demyelinating diseases have revealed alterations of connexin expr ession patterns in demyelinating lesions. To elucidate the molecular mechanisms of connexins in the pathomechanisms of inflammatory demyelination, we induced experimental autoimmune encephalomyelitis (EAE) in connexin 30 (Cx30)‐deficient mice, oligodendroglia‐specific Cx47‐ablated mice, and as troglia‐specific Cx43‐ablated mice. We found that both astroglial‐Cx30‐deficient mice and Cx43‐ablated mice showed amelioration of the clinical course of EAE, while oligodendroglial‐Cx47‐ablated mice showed aggravation. These findings indicate the distinct role of connexins expressed i n different cell types and the substantial contribution of connexin...
Source: Clinical and Experimental Neuroimmunology - Category: Neurology Authors: Tags: REVIEW ARTICLE Source Type: research

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Corticosteroids are effective therapy for autoimmune diseases but serious adverse effects preclude their prolonged use. However, immune-suppressive biologics that inhibit lymphoid proliferation are now in use as corticosteroid sparing-agents but with variable success; thus, the need to develop alternative immune-suppressive approaches including cell-based therapies. Efficacy of ex-vivo-generated IL-35-producing regulatory B-cells (i35-Bregs) in suppressing/ameliorating encephalomyelitis or uveitis in mouse models of multiple sclerosis or uveitis, respectively, is therefore a promising therapeutic approach for CNS autoimmun...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the CNS. Bile acids are cholesterol metabolites that can signal through receptors on cells throughout the body, including in the CNS and the immune system. Whether bile acid metabolism is abnormal in MS is unknown. Using global and targeted metabolomic profiling, we identified lower levels of circulating bile acid metabolites in multiple cohorts of adult and pediatric patients with MS compared with controls. In white matter lesions from MS brain tissue, we noted the presence of bile acid receptors on immune and glial cells. To mechanistically examine the ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
AbstractB cells are key players in humoral immune responses and have important roles in inflammatory diseases of the central nervous system (CNS). Accumulating evidence has indicated that antibody ‐independent B cell functions, antigen presentation to T cells, and the production of cytokines, are involved in the pathogenesis of CNS inflammatory diseases. However, the precise pathomechanisms of impaired B cell tolerance and production of autoantibodies against CNS autoantigens are still unkn own. In this review, we summarize the effector functions of B cells in the pathogenesis of the CNS autoimmune diseases, multiple scl...
Source: Clinical and Experimental Neuroimmunology - Category: Neurology Authors: Tags: REVIEW ARTICLE (INVITED) Source Type: research
Objective To review currently available data on the transfer of monoclonal antibodies (mAbs) in the breastmilk of women receiving treatment for neurologic and non-neurologic diseases. Methods We systematically searched the medical literature for studies referring to 19 selected mAb therapies frequently used in neurologic conditions and "breastmilk," "breast milk," "breastfeeding," or "lactation." From an initial list of 288 unique references, 29 distinct full-text studies met the eligibility criteria. One additional study was added after the literature search based on expert knowled...
Source: Neurology Neuroimmunology and Neuroinflammation - Category: Neurology Authors: Tags: Autoimmune diseases, Multiple sclerosis Views [amp ] Reviews Source Type: research
Authors: Chan VS Abstract Multiple sclerosis (MS) is an aggravating autoimmune disease that cripples young patients slowly with physical, sensory and cognitive deficits. The break of self-tolerance to neuronal antigens is the key to the pathogenesis of MS, with autoreactive T cells causing demyelination that subsequently leads to inflammation-mediated neurodegenerative events in the central nervous system. The exact etiology of MS remains elusive; however, the interplay of genetic and environmental factors contributes to disease development and progression. Given that genetic variation only accounts for a fraction ...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
AbstractThe idea that B  cells participate in immune regulation was initially postulated from observations in animals in the 1970s. It is now established that certain B‐cell populations, known as regulatory B cells, regulate immune reactions in various animal models of autoimmunity, chiefly through the production of in terleukin‐10. Subsequent to these findings in animals, several B‐cell subsets have been identified in human blood that are capable of producing interleukin‐10 when stimulatedex vivo. Although we still do not have direct evidence showing that these interleukin ‐10‐producing B cells ...
Source: Clinical and Experimental Neuroimmunology - Category: Neurology Authors: Tags: REVIEW ARTICLE Source Type: research
Basel, 22 May 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) will present new pooled pivotal satralizumab safety results for the treatment of neuromyelitis optica spectrum disorder (NMOSD), a rare, debilitating central nervous system disorder. These data are being presented at the 6th Annual Meeting of the European Academy of Neurology (EAN) and show satralizumab was well-tolerated in a broad patient population – including adolescents, for whom there is no approved medicine. Satralizumab is an investigational humanised monoclonal antibody that targets the interleukin-6 (IL-6) receptor, believed to play a key role in the i...
Source: Roche Media News - Category: Pharmaceuticals Source Type: news
Contributors : Li Wang ; Rong Qiu ; YangZhao Zhang ; Zhijun Han ; Chao Yao ; Guojun Hou ; Dai Dai ; Wenfei Jin ; Yuanjia Tang ; Xiang Yu ; Nan ShenSeries Type : Expression profiling by high throughput sequencingOrganism :Multiple sclerosis is a chronic autoimmune disease driven by pathogenic Th17 cells. Here, we dissected the role of miR-22 in pathogenic Th17 cells by autoantigen-specific disease models. We first showed that miR-22 was upregulated in peripheral lymphoid organs and spinal cords of mice developed autoimmune encephalomyelitis. Although miR-22 was upregulated in multiple helper T cell subsets, it was dispensab...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Source Type: research
Publication date: Available online 21 May 2020Source: Multiple Sclerosis and Related DisordersAuthor(s): Elizabeth R. Comini-Frota, Angelo Pontes Freitas Campos, Antonio Pereira Gomes Neto, Paulo Pereira Christo
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
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 75  mg/kg of oral CBD given for 5 days 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) we...
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research
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