MIP-3β/CCL19 is associated with the intrathecal invasion of mononuclear cells in neuroinflammatory and non-neuroinflammatory CNS diseases in dogs
TL;DR: CCL19 CSF concentrations were markedly elevated in patients affected with the neuroinflammatory diseasesSRMA and MUO and showed a strong correlation with the CSF cell count, suggesting this chemokine may play an important role in the pathogenesis of SRMA andMUO.
Abstract: Background
Chemokines such as MIP-3β/CCL19 are important factors in the mechanism of cell migration and pathogenesis of central nervous system (CNS) inflammatory reactions. The hypothesis of this study is that CCL19, also known as MIP-3β, is involved in the pathogenesis of inflammatory and non-inflammatory CNS diseases of dogs. Experiments were performed on cerebrospinal fluid (CSF) and serum samples of dogs affected with steroid responsive meningitis-arteritis (SRMA) during the acute phase as well as during treatment. Dogs with SRMA were compared to dogs with presumed meningoencephalomyelitis of unknown origin (MUO), and both groups sub-categorized into dogs receiving no therapy and with patients receiving prednisolone therapy. Idiopathic epilepsy (IE), a group with normal CSF cell count, was used as a control. Additionally, dogs with intervertebral disc disease (IVDD) of varying severity were analyzed. Chemokine concentrations were determined by enzyme linked immunosorbent assay. Migration assays were performed on seven selected CSF samples using a disposable 96-well chemotaxis chamber.
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01 Sep 2015
TL;DR: This dissertation evaluated the differences in genomic and genetic properties between duplicate copies in order to understand the effect duplication mechanisms may have on the divergence of duplicate pairs.
Abstract: Gene duplication is considered a major contributor to genome evolution and functional diversity. Differences in genomic features (such as structural resemblance, transcriptional orientation, and genomic location) between members of a gene duplicate pair may indicate the possible duplication mechanisms, as well as the evolutionary fates the paralogs may experience. In addition to these genomic features, molecular genetic features, such as differences in codon usage and expression levels may provide further insight into functional changes between paralogs. In this dissertation, multiple genomic analyses were conducted in order to evaluate the differences in genomic and genetic properties between duplicate copies in order to understand the effect duplication mechanisms may have on the divergence of duplicate pairs. Chapter Two focuses on differing patterns of sequence asymmetry, codon usage, and gene expression levels between the members of gene duplicate pairs belonging to two different populations of paralogs in Saccharomyces cerevisiae: ohnologs, which arose via a whole genome duplication (WGD), and small segmental duplication (SSD)
1 citations
TL;DR: There remains until recently an overall lack of clarity for the practical criteria for the diagnosis of canine idiopathic epilepsy but the emerge of new diagnostic methods, such as cerebrospinal fluid and/or serum biomarkers, advanced functional neuroimaging techniques and electroencephalography, is likely to change the diagnostic approach in canine epilepsy in the near future.
Abstract: Clinical bottom line There remains until recently an overall lack of clarity for the practical criteria for the diagnosis of canine idiopathic epilepsy. Signalment and an interictal neurological examination are vital for the diagnosis of idiopathic epilepsy. Despite the current insufficient evidence, the emerge of new diagnostic methods, such as cerebrospinal fluid and/or serum biomarkers, advanced functional neuroimaging techniques and electroencephalography, is likely to change the diagnostic approach in canine epilepsy in the near future.
Cites background from "MIP-3β/CCL19 is associated with the..."
...Bartels (2014) Population: Dogs with SRMA, MUO, IVDD, idiopathic epilepsy (Tier I) and healthy dogs....
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References
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TL;DR: Current understanding of the roles played by chemokines in the functional biology of secondary lymphoid organs will be reviewed and a central role for the chemokine family of molecules has been uncovered.
Abstract: As few as one in 100,000 B and T lymphocytes are specific for a single protein antigen, such as tetanus toxin, yet these cells must come together if an antibody response is to occur. Bringing antigen-presenting cells and rare antigen-specific B and T lymphocytes into physical contact is a principal function of secondary lymphoid organs. In the last few years, details have begun to emerge on the cues that guide cell movements inside lymphoid organs, and a central role for the chemokine family of molecules has been uncovered. Here, current understanding of the roles played by chemokines in the functional biology of secondary lymphoid organs will be reviewed.
1,064 citations
"MIP-3β/CCL19 is associated with the..." refers background in this paper
...CCL19 is constitutively expressed in the CNS for fast immunosurveillance [11] and is produced by different cells such as dendritic cells (DC), macrophages and some non-hematopoietic cells [11,12]....
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TL;DR: The immune system is composed of single cells, and its function is entirely dependent on the capacity of these cells to traffic, localize within tissues, and interact with each other in a precisely coordinated fashion.
Abstract: The immune system is composed of single cells, and its function is entirely dependent on the capacity of these cells to traffic, localize within tissues, and interact with each other in a precisely coordinated fashion. There is growing evidence that the large families of chemokines and chemokine receptors provide a flexible code for regulating cell traffic and positioning in both homeostatic and inflammatory conditions. The regulation of chemokine receptor expression during development and following cell activation explains the complex migratory pathways taken by dendritic cells, T and B lymphocytes, providing new insights into the mechanisms that control priming, effector function, and memory responses.
1,042 citations
TL;DR: A novel chemokine-dependent reciprocal cross-talk between neutrophils and Th17 cells is revealed, which may represent a useful target for the treatment of chronic inflammatory diseases.
695 citations
"MIP-3β/CCL19 is associated with the..." refers background in this paper
...Activated neutrophils induced chemotaxis of Th17 cells and in turn could attract more neutrophils [35]....
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...’s study revealed that a novel chemokine-dependent reciprocal cross-talk between neutrophils and Th17 cells exists [35]....
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TL;DR: Insight is provided into the mechanisms that control T-cell priming as well as memory and effector immune responses, following antigenic stimulation.
Abstract: The immune response requires a timely interaction among different cell types within distinct microenvironments. Our studies have focused on the regulation of chemokine receptors in dendritic cells (DC) and T lymphocytes. Chemokine receptors expressed by immature DC promote their migration to inflamed tissues, where antigens are captured and maturation is induced. Maturing DC upregulate CCR7, which drives their migration to the T-cell areas of the draining lymph nodes where antigen is presented to naive T cells. DC produce a variety of chemokines that influence DC recruitment into inflamed tissues and DC-T-cell interaction in the lymph nodes. Chemokine receptors are differentially acquired by developing Th1 and Th2 cells and are differentially expressed on subsets of "central memory" and "effector memory" T cells. Furthermore, following antigenic stimulation, effector T cells can rapidly switch chemokine receptor expression, acquiring new migratory capacities. These studies provide insights into the mechanisms that control T-cell priming as well as memory and effector immune responses.
538 citations
"MIP-3β/CCL19 is associated with the..." refers background in this paper
...It binds to the CCR7 receptor which is expressed on myeloid cells [13], mature DC, T cells, as well as activated B cells [14-16]....
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TL;DR: Results indicate that following SCI, all classes of neural cells initially contribute to the organization of inflammation, whereas recruited immune cells mostly contribute to its maintenance at later time points.
Abstract: We have studied the spatial and temporal distribution of six proinflammatory cytokines and identified their cellular source in a clinically relevant model of spinal cord injury (SCI). Our findings show that interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF) are rapidly (<5 and 15 minutes, respectively) and transiently expressed in mice following contusion. At 30-45 minutes post SCI, IL-1beta and TNF-positive cells could already be seen over the entire spinal cord segment analyzed. Multilabeling analyses revealed that microglia and astrocytes were the two major sources of IL-1beta and TNF at these times, suggesting a role for these cytokines in gliosis. Results obtained from SCI mice previously transplanted with green fluorescent protein (GFP)-expressing hematopoietic stem cells confirmed that neural cells were responsible for the production of IL-1beta and TNF for time points preceding 3 hours. From 3 hours up to 24 hours, IL-1beta, TNF, IL-6, and leukemia inhibitory factor (LIF) were strongly upregulated within and immediately around the contused area. Colocalization studies revealed that all populations of central nervous system resident cells, including neurons, synthesized cytokines between 3 and 24 hours post SCI. However, work done with SCI-GFP chimeric mice revealed that at least some infiltrating leukocytes were responsible for cytokine production from 12 hours on. By 2 days post-SCI, mRNA signal for all the above cytokines had nearly disappeared. Notably, we also observed another wave of expression for IL-1beta and TNF at 14 days. Overall, these results indicate that following SCI, all classes of neural cells initially contribute to the organization of inflammation, whereas recruited immune cells mostly contribute to its maintenance at later time points.
537 citations
"MIP-3β/CCL19 is associated with the..." refers background in this paper
...A study from Pineau and Lacroix on rodent models revealed that cytokine production is time dependent [43]....
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...This would suggest that neural cells are responsible for the initial inflammatory response following SCI but, the recruitment of additional immune cells is responsible for the maintenance of inflammation [43]....
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