scholarly journals Nasal delivery of Fasudil-modified immune cells exhibits therapeutic potential in experimental autoimmune encephalomyelitis

2019 ◽  
Vol 25 (6) ◽  
pp. 783-795
Author(s):  
Shang-De Guo ◽  
Chun-Yun Liu ◽  
Jing-Wen Yu ◽  
Zhi Chai ◽  
Qing Wang ◽  
...  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Thais Fernanda de Campos Fraga-Silva ◽  
Luiza Ayumi Nishiyama Mimura ◽  
Larissa Ragozo Cardoso de Oliveira ◽  
Juliana Helena dos Santos Toledo ◽  
Patrícia Aparecida Borim ◽  
...  

AbstractMultiple sclerosis is an autoimmune disease that affects the myelinated central nervous system (CNS) neurons and triggers physical and cognitive disabilities. Conventional therapy is based on disease-modifying drugs that control disease severity but can also be deleterious. Complementary medicines have been adopted and evidence indicates that yeast supplements can improve symptoms mainly by modulating the immune response. In this investigation, we evaluated the therapeutic potential of Saccharomyces cerevisiae and its selenized derivative (Selemax) in experimental autoimmune encephalomyelitis (EAE). Female C57BL/6 mice submitted to EAE induction were orally supplemented with these yeasts by gavage from day 0 to day 14 after EAE induction. Both supplements determined significant reduction in clinical signs concomitantly with diminished Th1 immune response in CNS, increased proportion of Foxp3+ lymphocytes in inguinal and mesenteric lymph nodes and increased microbiota diversity. However, Selemax was more effective clinically and immunologically; it reduced disease prevalence more sharply, increased the proportion of CD103+ dendritic cells expressing high levels of PD-L1 in mesenteric lymph nodes and reduced the intestinal inflammatory process more strongly than S. cerevisiae. These results suggest a clear gut-brain axis modulation by selenized S. cerevisiae and suggest their inclusion in clinical trials.


Author(s):  
Sarah Dhaiban ◽  
Mena Al-Ani ◽  
Noha Mousaad Elemam ◽  
Mahmood H Al-Aawad ◽  
Zeinab Al-Rawi ◽  
...  

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by varying degrees of demyelination of uncertain etiology, and is associated with specific environmental and genetic factors. Upon recognition of CNS antigens, the immune cells initiate an inflammatory process which leads to destruction and deterioration of the neurons. Innate immune cells such as macrophages, dendritic cells and natural killer cells are known to play critical roles in the pathogenesis of MS. Also, the activation of peripheral CD4+ T cells by CNS antigens leads to their extravasation into the CNS causing damages that exacerbates the disease. This could be accompanied by dysregulation of T regulatory cells and other cell types functions. Experimental autoimmune encephalomyelitis (EAE) is a mouse model used to study the pathophysiology of MS disease. In this review, we highlight the roles of innate and adaptive immune players in the pathogenesis of MS and EAE.


2015 ◽  
Vol 6 ◽  
Author(s):  
Fernández Hurst Nicolás ◽  
Falcón Cristian ◽  
Rupil Lucía ◽  
Cervi Laura ◽  
Monferran Clara ◽  
...  

Brain ◽  
2019 ◽  
Vol 142 (10) ◽  
pp. 2979-2995 ◽  
Author(s):  
Barbara Morquette ◽  
Camille A Juźwik ◽  
Sienna S Drake ◽  
Marc Charabati ◽  
Yang Zhang ◽  
...  

Dysregulation of miRNAs has been observed in many neurodegenerative diseases, including multiple sclerosis. Morquette et al. show that overexpression of miR-223-3p prevents accumulation of axonal damage in a rodent model of multiple sclerosis, in part through regulation of glutamate receptor signalling. Manipulation of miRNA levels may have therapeutic potential.


2019 ◽  
Vol 20 (7) ◽  
pp. 1793 ◽  
Author(s):  
Michael Valitsky ◽  
Sandrine Benhamron ◽  
Keren Nitzan ◽  
Dimitrios Karussis ◽  
Ezra Ella ◽  
...  

The complexity of central nervous system (CNS) degenerative/inflammatory diseases and the lack of substantially effective treatments point to the need for a broader therapeutic approach to target multiple components involved in the disease pathogenesis. We suggest a novel approach directed for the elimination of pathogenic agents from the CNS and, in parallel, its enrichment with an array of neuroprotective substances, using a “cerebrospinal fluid (CSF) exchange” procedure, in which endogenous (pathogenic) CSF is removed and replaced by artificial CSF (aCSF) enriched with secretions of human mesenchymal stem cells (MSCs). MSCs produce a variety of neuroprotective agents and have shown beneficial effects when cells are transplanted in animals and patients with CNS diseases. Our data show that MSCs grown in aCSF secrete neurotrophic factors, anti-inflammatory cytokines, and anti-oxidant agents; moreover, MSC-secretions-enriched-aCSF exerts neuroprotective and immunomodulatory effects in neuronal cell lines and spleen lymphocytes. Treatment of experimental-autoimmune-encephalomyelitis (EAE) mice with this enriched-aCSF using an intracerebroventricular (ICV) CSF exchange procedure (“CSF exchange therapy”) caused a significant delay in the onset of EAE and amelioration of the clinical symptoms, paralleled by a reduction in axonal damage and demyelination. These findings point to the therapeutic potential of the CSF exchange therapy using MSC-secretions-enriched-aCSF in inflammatory/degenerative diseases of the CNS.


2004 ◽  
Vol 200 (3) ◽  
pp. 345-351 ◽  
Author(s):  
Elisabeth Zinser ◽  
Matthias Lechmann ◽  
Antje Golka ◽  
Manfred B. Lutz ◽  
Alexander Steinkasserer

CD83 is up-regulated on the surface of dendritic cells (DCs) during maturation and has been widely used as a marker for mature DCs. Recently, we reported the recombinant expression of the extracellular immunoglobulin domain of human CD83 (hCD83ext). Using this soluble form of CD83, allogeneic as well as specific cytotoxic T lymphocyte proliferation could be blocked in vitro. Here we report the functional analysis of soluble CD83 in vivo, using murine experimental autoimmune encephalomyelitis (EAE) as a model. Strikingly, only three injections of soluble CD83 prevented the paralysis associated with EAE almost completely. In addition, even when the EAE was induced a second time, CD83-treated mice were protected, indicating a long-lasting suppressive effect. Furthermore, soluble CD83 strongly reduced the paralysis in different therapeutic settings. Most important, even when the treatment was delayed until the disease symptoms were fully established, soluble CD83 clearly reduced the paralyses. In addition, also when EAE was induced a second time, soluble CD83-treated animals showed reduced disease symptoms. Finally, hCD83ext treatment almost completely reduced leukocyte infiltration in the brain and in the spinal cord. In summary, this work strongly supports an immunosuppressive role of soluble CD83, thereby indicating its therapeutic potential in the regulation of immune disorders in vivo.


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