Search results for: Iain L. Campbell
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Microglia are the resident macrophages of the central nervous system (CNS). They are a heterogenous, exquisitely responsive, and highly plastic cell population, which enables them to perform diverse roles. They sense and respond to the local production of many different signals, including an assorted range of cytokines. Microglia respond strongly to interleukin‐6 (IL‐6) and members of the type I interferon...
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Molecular Neurobiology > 2019 > 56 > 12 > 7977-7993
Interleukin 23 (IL-23) is a key mediator in neuroinflammation in numerous autoimmune diseases including multiple sclerosis (MS). However, the pathophysiology of IL-23 and how it contributes to neuroinflammation is poorly defined. To further clarify the role of IL-23 in CNS inflammation, we generated a transgenic mouse model (GF-IL23) with astrocyte-targeted expression of both IL-23 subunits, IL-23p19,...
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Type I interferons (IFN‐I) are crucial for effective antimicrobial defense in the central nervous system (CNS) but also can cause severe neurological disease (termed cerebral interferonopathy) as exemplified by Aicardi‐Goutières Syndrome. In the CNS, microglia and astrocytes have essential roles in host responses to infection and injury, with both cell types responding to IFN‐I. While the IFN‐I signaling...
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Journal of Neuroimmunology > 2017 > 310 > C > 97-102
Cerebellar pathology is a frequent feature of multiple sclerosis (MS), a demyelinating and neuroinflammatory disease of the central nervous system (CNS). Interleukin (IL)-6 is a multifunctional cytokine with a potential role in MS. Here we studied cuprizone-induced cerebellar pathology in transgenic mice with astrocyte-targeted production of IL-6 (GFAP-IL6), specifically focusing on demyelination,...
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Molecular Neurobiology > 2018 > 55 > 2 > 946-957
Recent evidence suggests a pivotal role of the proinflammatory cytokine interleukin - 17A (IL-17) in demyelinating autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis (MS). Nevertheless, it remains unclear if this cytokine exerts direct effects on CNS resident cells during MS or modulates the function of infiltrating immune cells towards a more detrimental phenotype...
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Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Interleukin (IL)−6 is a pleiotropic cytokine with a potential role in MS. Here we used transgenic mice with astrocyte‐targeted production of IL‐6 (GFAP‐IL6Tg) to study the effect of IL‐6 in the cuprizone‐induced demyelination paradigm, which is an experimental model of de‐ and re‐myelination, both hallmarks of...
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The gp130 cytokines include IL-6, IL-11, LIF and OSM. These cytokines have important roles in neuroinflammation and neurodevelopment. However, the nature of any cell-specific responses of astrocytes and microglia to this cytokine family and their molecular basis is not well understood. Here, the gp130 family cytokine signal pathway activation and global transcriptional responses were examined in murine...
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Functional type I interferon (IFN-I) signalling is critical for the host response to viruses. Cellular responses to IFN-Is depend largely on STAT1, STAT2 and IRF9. Here we studied the effects of IRF9 deficiency on the host response to a viral infection in the CNS. Wild-type (WT) mice and mice lacking IRF9 (IRF9 KO) were infected intracranially with Lymphocytic Choriomeningitis Virus (LCMV). In WT...
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We have shown that following systemic infection with lymphocytic choriomeningitis virus (LCMV), STAT1 KO but not WT, IFNAR KO, STAT1/IFNAR DKO, STAT2 KO or STAT1/STAT2 DKO mice develop type I-IFN-dependent, CD4+ T-cell-mediated lethal disease. Here we determined the underlying molecular mechanisms of this disease. Following infection, higher levels of LCMV were observed in peripheral organs of all...
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Interleukin‐6 (IL‐6) participates in the host response to injury and infection in the central nervous system (CNS). We identified strawberry notch homolog 2 (Sbno2) as an IL‐6‐stimulated gene in murine astrocytes. Sbno2 is a mouse homolog of the sno gene in Drosophila but little is known about the regulation or function of the mammalian gene. Here we examined the regulation of the Sbno2 gene in astrocytes...
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Interleukin‐10 (IL‐10) is a cytokine that plays a crucial role in regulating the inflammatory response and immune reactions. In the central nervous system (CNS), IL‐10 is mainly produced by astrocytes and microglia and it is upregulated after various insults, such as experimental autoimmune encephalomyelitis, middle cerebral artery occlusion, excitotoxicity and traumatic brain injury. To better understand...
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Brain Behavior and Immunity > 2015 > 45 > Complete > 80-97
Interleukin-10 (IL-10) is a cytokine classically linked with anti-inflammatory and protective functions in the central nervous system (CNS) in different neurodegenerative and neuroinflammatory conditions. In order to study the specific role of local CNS produced IL-10, we have created a new transgenic mouse line with astrocyte-targeted production of IL-10 (GFAP-IL10Tg). In the present study, the effects...
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Journal of Autoimmunity > 2014 > 55 > Complete > 24-32
Inflammatory mechanisms play a key role in the pathogenesis of type 1 and type 2 diabetes. IL6, a pleiotropic cytokine with impact on immune and non-immune cell types, has been proposed to be involved in the events causing both forms of diabetes and to play a key role in experimental insulin-dependent diabetes development. The aim of this study was to investigate how beta-cell specific overexpression...
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The interleukin (IL)‐6/gp130 family of cytokines (e.g., IL‐6, IL‐11, leukemia inhibitory factor (LIF) and oncostatin M (OSM)) play important roles in the central nervous system (CNS) during neuroinflammation and neurodevelopment. However, little is known regarding the responses by astroglia and microglia to this family of cytokines. Here the expression of the IL‐6/gp130 cytokine receptors and subsequent...
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Canonical type I interferon (IFN-I) signaling through interferon stimulated gene factor (ISGF) 3 has a key role in host innate and adaptive immune responses during viral infection. We have previously found that following systemic infection with lymphocytic choriomeningitis virus (LCMV), STAT1 KO but not WT, IFNAR KO or STAT1/IFNAR DKO mice develop lethal disease characterized by a ‘cytokine storm’...
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The gp130 cytokines, including IL-6, IL-11, LIF and OSM, have important roles in neuroinflammation and neurodevelopment. However, the nature of any cell-specific responses of astrocytes and microglia to this family of cytokines and their molecular basis are not well understood. Here, the expression of the gp130 family cytokine receptors and subsequent signal pathway activation were examined in murine...
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The transcription factor interferon regulatory factor (IRF) 8 has a key role in the cellular response to IFN-γ and is involved in myeloid cell differentiation. We have previously identified IRF8 to be a constitutive and IFN-γ-stimulated nuclear factor that regulates the homeostatic properties of microglia. Our study aimed to determine the role of IRF8 in the microglial response to sterile neuronal...
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