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Project description:Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that primarily affects the optic nerve and spinal cord within the central nervous system (CNS). Acute astrocyte injury caused by autoantibodies against aquaporin 4 (NMO-IgG) is a well-established key factor in the pathogenesis, ultimately leading to neuronal damage and patient disability. In addition to these humoral immune processes, numerous innate immune cells were found in the acute lesions of NMO patients. However, the origin and function of these innate immune cells remain unclear in NMO pathogenesis. Therefore, this study aims to analyze the origin and functions of these innate immune cells in an NMO-like mouse model and evaluate their role in the pathophysiology of NMO. The expression of Tmem119 on Iba1 + cells in brain tissue disappeared immediately after the injection of NMO-IgG + human complement mixture, while the expression of P2ry12 remained well-maintained at 1 day after injection. Based on these observations, it was demonstrated that monocytes infiltrate the brain during the early stages of the pathological process and are closely associated with the inflammatory response through the expression of the proinflammatory cytokine IL-1β. Understanding the variations in the expression patterns of P2ry12, Tmem119, and other markers could be helpful in distinguishing between these cell types and further analyzing their functions. Therefore, this research may contribute to a better understanding of the mechanisms and potential treatments for NMO.
| S-EPMC10786844 | biostudies-literature
Project description:Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that primarily affects the spinal cord and optic nerves in the central nervous system (CNS). It is characterized by the presence of immunoglobulin G (IgG) antibodies against aquaporin 4, a protein found in astrocytes (known as NMO-IgG). Monocytes/macrophages and microglia accumulate at the active injury sites and contribute to the disease process. However, it is unclear whether these active cells originate from circulating monocytes/macrophages or resident microglia. Recent studies have investigated the role of microglia/macrophages in multiple sclerosis (MS) using specific microglial markers, such as P2ry12 and Tmem119, and have shown that active cells are derived from microglia. In contrast, the function of monocyte/macrophages and microglia in NMO has not been extensively studied. Therefore, this study aims to analyze the functions of monocytes/macrophages and microglia using microglial markers (P2ry12 and Tmem119) in an NMO-like mouse model and evaluate their role in the pathophysiology of NMO.
2024-01-17 | GSE235277 | GEO
Project description:Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that primarily affects the spinal cord and optic nerves in the central nervous system (CNS). It is characterized by the presence of immunoglobulin G (IgG) antibodies against aquaporin 4, a protein found in astrocytes (known as NMO-IgG). Monocytes/macrophages and microglia accumulate at the active injury sites and contribute to the disease process. However, it is unclear whether these active cells originate from circulating monocytes/macrophages or resident microglia. Recent studies have investigated the role of microglia/macrophages in multiple sclerosis (MS) using specific microglial markers, such as P2ry12 and Tmem119, and have shown that active cells are derived from microglia. In contrast, the function of monocyte/macrophages and microglia in NMO has not been extensively studied. Therefore, this study aims to analyze the functions of monocytes/macrophages and microglia using microglial markers (P2ry12 and Tmem119) in an NMO-like mouse model and evaluate their role in the pathophysiology of NMO.
2024-01-17 | GSE235276 | GEO
Project description:Early Involvement of Peripherally Derived Monocytes in Inflammation in an NMO-Like Mouse Model [Monocytes]
| PRJNA985646 | ENA
Project description:Early Involvement of Peripherally Derived Monocytes in Inflammation in an NMO-Like Mouse Model
| PRJNA985638 | ENA
Project description:Early Involvement of Peripherally Derived Monocytes in Inflammation in an NMO-Like Mouse Model [microglia]
| PRJNA985645 | ENA
Project description:Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disease of the central nervous system that affects motor function and causes relapsing disability. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been used extensively in the treatment of various inflammatory diseases, due to their potent regulatory roles that can mitigate inflammation and repair damaged tissues. However, their use in NMO is currently limited, and the mechanism underlying the beneficial effects of hUC-MSCs on motor function in NMO remains unclear. In this study, we investigate the effects of hUC-MSCs on the recovery of motor function in an NMO systemic model. Our findings demonstrate that milk fat globule epidermal growth 8 (MFGE8), a key functional factor secreted by hUC-MSCs, plays a critical role in ameliorating motor impairments. We also elucidate that the MFGE8/Integrin αvβ3/NF-κB signaling pathway is partially responsible for structural and functional recovery, in addition to motor functional enhancements induced by hUC-MSC exposure. Taken together, these findings strongly support the involvement of MFGE8 in mediating hUC-MSCs-induced improvements in motor functional recovery in an NMO mouse model. In addition, this provides new insight on the therapeutic potential of hUC-MSCs and the mechanisms underlying their beneficial effects in NMO.
| S-EPMC10798960 | biostudies-literature
Project description:Infiltrating monocyte-derived macrophages (MDMs) and resident microglia dominate central nervous system (CNS) injury sites. Differential roles for these cell populations after injury are beginning to be uncovered. Here, we show evidence that MDMs and microglia directly communicate with one another and differentially modulate each other's functions. Importantly, microglia-mediated phagocytosis and inflammation are suppressed by infiltrating macrophages. In the context of spinal cord injury (SCI), preventing such communication increases microglial activation and worsens functional recovery. We suggest that macrophages entering the CNS provide a regulatory mechanism that controls acute and long-term microglia-mediated inflammation, which may drive damage in a variety of CNS conditions.
| S-EPMC6205650 | biostudies-literature
Project description:Traumatic brain injury (TBI) is a leading cause for neurological disabilities world-wide. TBI occurs most frequently among the elderly population, and elderly TBI survivors suffer from reduced recovery and poorer quality of life. The effect of age on the pathophysiology of TBI is still poorly understood. We previously established that peripherally-derived monocytes (CCR2⁺) infiltrate the injured brain and contribute to chronic TBI-induced cognitive deficits in young animals. Furthermore, age was shown to amplify monocyte infiltration acutely after injury. In the current study, we investigated the impact of age on the subchronic response of peripherally-derived monocytes (CD45hi; CCR2⁺) and their role in the development of chronic cognitive deficits. In the aged brain, there was a significant increase in the number of peripherally-derived monocytes after injury compared to young, injured animals. The infiltration rate of peripherally-derived monocytes remained elevated subchronically and corresponded with enhanced expression of CCR2 chemotactic ligands. Interestingly, the myeloid cell populations observed in injured aged brains had impaired anti-inflammatory responses compared to those in young animals. Additionally, in the aged animals, there was an expansion of the blood CCR2⁺ monocyte population after injury that was not present in the young animals. Importantly, knocking out CCR2 to inhibit infiltration of peripherally-derived monocytes prevented chronic TBI-induced spatial memory deficits in the aged mice. Altogether, these results demonstrate the critical effects of age on the peripherally-derived monocyte response during the progression of TBI pathophysiology.
| S-EPMC6032263 | biostudies-literature
Project description:The metabolic intermediate of acetaminophen (APAP) can cause severe hepatocyte necrosis, which triggers aberrant immune activation of liver non-parenchymal cells (NPC). Overzealous hepatic inflammation determines the morbidity and mortality of APAP-induced liver injury (AILI). Interleukin-1 receptor (IL-1R) signaling has been shown to play a critical role in various inflammatory conditions, but its precise role and underlying mechanism in AILI remain debatable. Herein, we show that NLRP3 inflammasome activation of IL-1? is dispensable to AILI, whereas IL-1?, the other ligand of IL-1R1, accounts for hepatic injury by a lethal dose of APAP. Furthermore, Kupffer cells function as a major source of activated IL-1? in the liver, which is activated by damaged hepatocytes through TLR4/MyD88 signaling. Finally, IL-1? is able to chemoattract and activate CD11b+Gr-1+ myeloid cells, mostly neutrophils and inflammatory monocytes, to amplify deteriorated inflammation in the lesion. Therefore, this work identifies that MyD88-dependent activation of IL-1? in Kupffer cells plays a central role in the immunopathogenesis of AILI and implicates that IL-1? is a promising therapeutic target for AILI treatment.
| S-EPMC6207754 | biostudies-literature