scholarly journals AIM2 controls microglial inflammation to prevent experimental autoimmune encephalomyelitis

2021 ◽  
Vol 218 (5) ◽  
Author(s):  
Chunmei Ma ◽  
Sheng Li ◽  
Yingchao Hu ◽  
Yan Ma ◽  
Yuqing Wu ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Family Member ◽  
Immune Cells ◽  
Inflammasome Activation ◽  
Autoimmune Encephalomyelitis ◽  
Independent Mechanism ◽  
Peripheral Immune Cells ◽  
Microglial Inflammation ◽  
Experimental Autoimmune

The role of the PYHIN family member absent in melanoma 2 (AIM2), another important inflammasome sensor, in EAE remains unclear. In this study, we found that AIM2 negatively regulates the pathogenesis of EAE independent of inflammasome activation. AIM2 deficiency enhanced microglia activation and infiltration of peripheral immune cells into the CNS, thereby promoting neuroinflammation and demyelination during EAE. Mechanistically, AIM2 negatively regulates the DNA-PK–AKT3 in microglia to control neuroinflammation synergistically induced by cGAS and DNA-PK. Administration of a DNA-PK inhibitor reduced the severity of the EAE. Collectively, these findings identify a new role for AIM2 in controlling the onset of EAE. Furthermore, delineation of the underlying inflammasome-independent mechanism highlights cGAS and DNA-PK signaling as potential targets for the treatment of heterogeneous MS.

scholarly journals Role of Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

2020 ◽  
Author(s):  
Sarah Dhaiban ◽  
Mena Al-Ani ◽  
Noha Mousaad Elemam ◽  
Mahmood H Al-Aawad ◽  
Zeinab Al-Rawi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cells ◽  
T Regulatory Cells ◽  
Cell Types ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Chronic Autoimmune Disease ◽  
Experimental Autoimmune

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.

PGE2/EP4 signaling in peripheral immune cells promotes development of experimental autoimmune encephalomyelitis

2014 ◽  
Vol 87 (4) ◽  
pp. 625-635 ◽  
Author(s):  
Susanne Schiffmann ◽  
Andreas Weigert ◽  
Julia Männich ◽  
Max Eberle ◽  
Kerstin Birod ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cells ◽  
Autoimmune Encephalomyelitis ◽  
Peripheral Immune Cells ◽  
Experimental Autoimmune

scholarly journals Role of Peripheral Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 12
Author(s):  
Sarah Dhaiban ◽  
Mena Al-Ani ◽  
Noha Mousaad Elemam ◽  
Mahmood H. Al-Aawad ◽  
Zeinab Al-Rawi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cells ◽  
Autoimmune Encephalomyelitis ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Exact Etiology ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the myelination of the neurons present in the central nervous system (CNS). The exact etiology of MS development is unclear, but various environmental and genetic factors might play a role in initiating the disease. Experimental autoimmune encephalomyelitis (EAE) is a mouse model that is used to study the pathophysiology of MS disease as well as the effects of possible therapeutic agents. In addition, autoreactive immune cells trigger an inflammatory process upon the recognition of CNS antigens, which leads to destruction of the neurons. These include innate immune cells such as macrophages, dendritic cells, and natural killer cells. Additionally, the activation and extravasation of adaptive immune cells such as CD4+ T cells into the CNS may lead to further exacerbation of the disease. However, many studies revealed that immune cells could have either a protective or pathological role in MS. In this review, we highlight the roles of innate and adaptive immune cellular and soluble players that contribute to the pathogenesis of MS and EAE, which may be used as potential targets for therapy.

scholarly journals Gasdermin D in peripheral myeloid cells drives neuroinflammation in experimental autoimmune encephalomyelitis

2019 ◽  
Vol 216 (11) ◽  
pp. 2562-2581 ◽  
Author(s):  
Sheng Li ◽  
Yuqing Wu ◽  
Dongxue Yang ◽  
Chunyan Wu ◽  
Chunmei Ma ◽  
...  
Keyword(s):  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cells ◽  
Nlrp3 Inflammasome ◽  
Myeloid Cells ◽  
Autoimmune Encephalomyelitis ◽  
T Cell Infiltration ◽  
Secondary Lymphoid Organs ◽  
Experimental Autoimmune

The NLRP3 inflammasome is critical for EAE pathogenesis; however, the role of gasdermin D (GSDMD), a newly identified pyroptosis executioner downstream of NLRP3 inflammasome, in EAE has not been well defined. Here, we observed that the levels of GSDMD protein were greatly enhanced in the CNS of EAE mice, especially near the areas surrounding blood vessels. GSDMD was required for the pathogenesis of EAE, and GSDMD deficiency in peripheral myeloid cells impaired the infiltration of immune cells into the CNS, leading to the suppression of neuroinflammation and demyelination. Furthermore, the loss of GSDMD reduced the activation and differentiation of T cell in the secondary lymphoid organs and prevented T cell infiltration into CNS of EAE. The administration of inflammasome-related cytokines partially rescued the impairment of pathogenesis of EAE in GSDMD KO mice. Collectively, these findings provide the first demonstration of GSDMD in peripheral myeloid cells driving neuroinflammation during EAE pathogenesis.

scholarly journals Increase in MMP-9 Expressing CD11b+ cells in a CD44 Dependent Way Reduces Severity of Experimental Autoimmune Encephalomyelitis

2018 ◽  
Vol 14 (3) ◽  
pp. 147-149
Author(s):  
Sujata Kar ◽  
Kalipada Kar
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cells ◽  
Neurodegenerative Disorder ◽  
Cellular Adhesion ◽  
Phagocytic Cells ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Background: Multiple sclerosis (MS) is a dangerous neurodegenerative disorder. Various aspects of  the    disease have been studied in experimental animal model. Migration of immune cells to the central nervous system (CNS) is a predominant feature of MS. CD44 molecule has been reported to be involved in many  important biological processes including contribution in severing inflammation in experimental autoimmune encephalomyelitis (EAE). Matrix metalloprotease-9 (MMP-9) interaction with CD44 has been well known to be involved in cellular adhesion, transmigration and inflammation. In this study, we were interested to examine the role of phagocytic cells expressing MMP-9 in resolving EAE. Materials and Methods: C57BL/6 WT and CD44 KO mice were used as EAE animal model. The level of phagocytic cells expressing MMP-9 in the  secondary lymphoid organs were assessed in EAE induced WT as well as CD44 KO animals. Results: EAE severity was found in CD44 KO group compared to WT. Level of CD11b cells (marker of phagocytic cell) in the peritoneal cells expressing MMP-9 was higher in WT compared to CD44 KO. CD11b stained area found to be greater in WT lymph node compared to CD44 KO. Conclusions: This observation suggests the role of CD44 molecule in modulating the immune scenario which is related to disease severity. This study also opens avenues for the specific inflammatory roles of different immune cells in MS.Keywords: multiple sclerosis; EAE; CD44; MMP-9; CD11b; CNS. 

Role of alpha-metylacyl-CoA racemase in immune cells during the development of experimental autoimmune encephalomyelitis

2014 ◽  
Vol 275 (1-2) ◽  
pp. 121-122
Author(s):  
Nadja Tafferner ◽  
Julia Männich ◽  
Max Eberle ◽  
Nerea Ferreiros ◽  
Natasja Debruin ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cells ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals Role of the PD‐1/PD‐L1 Signaling in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Recent Insights and Future Directions

2021 ◽  
Author(s):  
Yan Mi ◽  
Jinming Han ◽  
Jie Zhu ◽  
Tao Jin
Keyword(s):  
Multiple Sclerosis ◽  
T Lymphocytes ◽  
Experimental Autoimmune Encephalomyelitis ◽  
B Lymphocytes ◽  
Immune Cells ◽  
Autoimmune Encephalomyelitis ◽  
Activated T Lymphocytes ◽  
The Central Nervous System ◽  
Experimental Autoimmune

AbstractMultiple sclerosis (MS) is an autoimmunity-related chronic demyelination disease of the central nervous system (CNS), causing young disability. Currently, highly specific immunotherapies for MS are still lacking. Programmed cell death 1 (PD-1) is an immunosuppressive co-stimulatory molecule, which is expressed on activated T lymphocytes, B lymphocytes, natural killer cells, and other immune cells. PD-L1, the ligand of PD-1, is expressed on T lymphocytes, B lymphocytes, dendritic cells, and macrophages. PD-1/PD-L1 delivers negative regulatory signals to immune cells, maintaining immune tolerance and inhibiting autoimmunity. This review comprehensively summarizes current insights into the role of PD-1/PD-L1 signaling in MS and its animal model experimental autoimmune encephalomyelitis (EAE). The potentiality of PD-1/PD-L1 as biomarkers or therapeutic targets for MS will also be discussed.

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