scholarly journals Astrocyte-specific expression of interleukin 23 leads to an aggravated phenotype and enhanced inflammatory response with B cell accumulation in the EAE model

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Louisa Nitsch ◽  
Simon Petzinna ◽  
Julian Zimmermann ◽  
Linda Schneider ◽  
Marius Krauthausen ◽  
...  

Abstract Background Interleukin 23 is a critical cytokine in the pathogenesis of multiple sclerosis. But the local impact of interleukin 23 on the course of neuroinflammation is still not well defined. To further characterize the effect of interleukin 23 on CNS inflammation, we recently described a transgenic mouse model with astrocyte-specific expression of interleukin 23 (GF-IL23 mice). The GF-IL23 mice spontaneously develop a progressive ataxic phenotype with cerebellar tissue destruction and inflammatory infiltrates with high amounts of B cells most prominent in the subarachnoid and perivascular space. Methods To further elucidate the local impact of the CNS-specific interleukin 23 synthesis in autoimmune neuroinflammation, we induced a MOG35-55 experimental autoimmune encephalomyelitis (EAE) in GF-IL23 mice and WT mice and analyzed the mice by histology, flow cytometry, and transcriptome analysis. Results We were able to demonstrate that local interleukin 23 production in the CNS leads to aggravation and chronification of the EAE course with a severe paraparesis and an ataxic phenotype. Moreover, enhanced multilocular neuroinflammation was present not only in the spinal cord, but also in the forebrain, brainstem, and predominantly in the cerebellum accompanied by persisting demyelination. Thereby, interleukin 23 creates a pronounced proinflammatory response with accumulation of leukocytes, in particular B cells, CD4+ cells, but also γδ T cells and activated microglia/macrophages. Furthermore, transcriptome analysis revealed an enhanced proinflammatory cytokine milieu with upregulation of lymphocyte activation markers, co-stimulatory markers, chemokines, and components of the complement system. Conclusion Taken together, the GF-IL23 model allowed a further breakdown of the different mechanisms how IL-23 drives neuroinflammation in the EAE model and proved to be a useful tool to further dissect the impact of interleukin 23 on neuroinflammatory models.

2014 ◽  
Vol 17 (3) ◽  
pp. 421-426 ◽  
Author(s):  
B. Tokarz-Deptuła ◽  
P. Niedźwiedzka-Rystwej ◽  
B. Hukowska-Szematowicz ◽  
M. Adamiak ◽  
A. Trzeciak-Ryczek ◽  
...  

Abstract In Poland, rabbit is a highly valued animal, due to dietetic and flavour values of its meat, but above all, rabbits tend to be commonly used laboratory animals. The aim of the study was developing standards for counts of B-cells with CD19+ receptor, T-cells with CD5+ receptor, and their subpopulations, namely T-cells with CD4+, CD8+ and CD25+ receptor in the peripheral blood of mixed-breed Polish rabbits with addition of blood of meet breeds, including the assessment of the impact of four seasons of the year and animal sex on the values of the immunological parameters determined. The results showed that the counts of B- and T-cells and their subpopulations in peripheral blood remain within the following ranges: for CD19+ B-cells: 1.05 - 3.05%, for CD5+ T-cells: 34.00 - 43.07%, CD4+ T-cells: 23.52 - 33.23%, CD8+ T-cells: 12.55 - 17.30%, whereas for CD25+ T-cells: 0.72 - 2.81%. As it comes to the season of the year, it was observed that it principally affects the values of CD25+ T-cells, while in the case of rabbit sex, more changes were found in females.


1995 ◽  
Vol 31 (10) ◽  
pp. 73-84 ◽  
Author(s):  
T. M. Iversen

The main environmental problems associated with fish farming in Denmark are attributable to the dam, the “dead reach” and nutrient and organic matter discharge. The environmental regulation of fish farming in Denmark started with the Environmental Protection Act of 1974, the Statutory Order of 1985 forbidding wet feed, and the Action Plan on the Aquatic Environment of 1987. In the case of freshwater fish farms, the latter was implemented through the measures stipulated in the 1989 Statutory Order on Fish Farms. The impact of Danish legislative measures to reduce and regulate the environmental effects of freshwater fish farms can be summarized as follows: - the number of fish farms has been reduced from about 800 in 1974 to about 500 at present; - production has tripled since 1974 and has been stable since 1989; - a change from wet to dry feed has reduced the environmental impact of the farms; - the national goals of the Action Plan on the Aquatic Environment of 1987 for reducing fish farm discharges of organic matter, nitrogen and phosphorus have been fulfilled. The main remaining problems are that: - the local impact of fish farms on downstream stream quality is still much too high in about 15% of cases; - the problem of the passage of migrating invertebrates and fish is still unsolved at some farms; - the problems posed by “dead reaches” are still unsolved. It is concluded that sustainable fish farming is possible in Denmark, but with the present technology production will have to be significantly reduced.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1480
Author(s):  
Hiresh Ayoubian ◽  
Joana Heinzelmann ◽  
Sebastian Hölters ◽  
Oybek Khalmurzaev ◽  
Alexey Pryalukhin ◽  
...  

Although microRNAs are described as promising biomarkers in many tumor types, little is known about their role in PSCC. Thus, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes considering the impact of HPV infection. In a first step, microarray analyses were performed on RNA from formalin-fixed, paraffin-embedded tumor (22), and normal (8) tissue samples. Microarray data were validated for selected miRNAs by qRT-PCR on an enlarged cohort, including 27 tumor and 18 normal tissues. We found 876 significantly differentially expressed miRNAs (p ≤ 0.01) between HPV-positive and HPV-negative tumor samples by microarray analysis. Although no significant differences were detected between normal and tumor tissue in the whole cohort, specific expression patterns occurred in distinct histological subtypes, such as HPV-negative usual PSCC (95 differentially expressed miRNAs, p ≤ 0.05) and HPV-positive basaloid/warty subtypes (247 differentially expressed miRNAs, p ≤ 0.05). Selected miRNAs were confirmed by qRT-PCR. Furthermore, microarray data revealed 118 miRNAs (p ≤ 0.01) that were significantly differentially expressed in metastatic versus non-metastatic usual PSCC. The lower expression levels for miR-137 and miR-328-3p in metastatic usual PSCC were validated by qRT-PCR. The results of this study confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV-dependent pathways.


2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.


2021 ◽  
Vol 60 (1) ◽  
pp. 145-157
Author(s):  
Yi Luo ◽  
Ke Yuan ◽  
Lumin Shen ◽  
Jiefu Liu

Abstract In this study, a series of in-plane hexagonal honeycombs with different Poisson's ratio induced by topological diversity are studied, considering re-entrant, semi-re-entrant and convex cells, respectively. The crushing strength of honeycomb in terms of Poisson's ratio is firstly presented. In the previous research, we have studied the compression performance of honeycomb with different negative Poisson's ratio. In this study, a comparative study on the local impact resistance of different sandwich panels is conducted by considering a spherical projectile with low to medium impact speed. Some critical criteria (i.e. local indentation profile, global deflection, impact force and energy absorption) are adopted to analyze the impact resistance. Finally, an influential mechanism of Poisson's ratio on the local impact resistance of sandwich panel is studied by considering the variation of core strength and post-impact collapse behavior.


2021 ◽  
pp. 1-8
Author(s):  
Costanza Ferrari Bardile ◽  
Harwin Sidik ◽  
Reynard Quek ◽  
Nur Amirah Binte Mohammad Yusof ◽  
Marta Garcia-Miralles ◽  
...  

Background: The relative contribution of grey matter (GM) and white matter (WM) degeneration to the progressive brain atrophy in Huntington’s disease (HD) has been well studied. The pathology of the spinal cord in HD is comparatively less well documented. Objective: We aim to characterize spinal cord WM abnormalities in a mouse model of HD and evaluate whether selective removal of mutant huntingtin (mHTT) from oligodendroglia rescues these deficits. Methods: Histological assessments were used to determine the area of GM and WM in the spinal cord of 12-month-old BACHD mice, while electron microscopy was used to analyze myelin fibers in the cervical area of the spinal cord. To investigate the impact of inactivation of mHTT in oligodendroglia on these measures, we used the previously described BACHDxNG2Cre mouse line where mHTT is specifically reduced in oligodendrocyte progenitor cells. Results: We show that spinal GM and WM areas are significantly atrophied in HD mice compared to wild-type controls. We further demonstrate that specific reduction of mHTT in oligodendroglial cells rescues the atrophy of spinal cord WM, but not GM, observed in HD mice. Inactivation of mHTT in oligodendroglia had no effect on the density of oligodendroglial cells but enhanced the expression of myelin-related proteins in the spinal cord. Conclusion: Our findings demonstrate that the myelination abnormalities observed in brain WM structures in HD extend to the spinal cord and suggest that specific expression of mHTT in oligodendrocytes contributes to such abnormalities.


1974 ◽  
Vol 28 (2) ◽  
pp. 153-178 ◽  
Author(s):  
Susan J. Koch

The aim of this study is to analyze the impact of the EEC on one border region, the French province of Alsace, through an examination of its economic and social transactions with West Germany since 1960. No great increase in Alsatian social ties with Germany has been observed, but there has been considerable growth in economic contacts, leading to a new prosperity for the province. Alsatian economic integration with the rest of France is not increasing as fast, but it has not been noticeably weakened. Alsatian elite and public opinion generally supports the growth of economic bonds with Germany, largely because of their contribution to economic welfare. Transaction and attitude data indicate a continuation of the present trend of important economic, but only limited social, ties between Alsace and its German neighbor.


2001 ◽  
Vol 107 (2) ◽  
pp. 359-366 ◽  
Author(s):  
Amy L. Woodward ◽  
Jonathan M. Spergel ◽  
Harri Alenius ◽  
Emiko Mizoguchi ◽  
Atul K. Bhan ◽  
...  

2017 ◽  
Vol 8 ◽  
Author(s):  
Itziar Ubillos ◽  
Joseph J. Campo ◽  
Pilar Requena ◽  
Maria Ome-Kaius ◽  
Sarah Hanieh ◽  
...  

1998 ◽  
Vol 4 (3) ◽  
pp. 162-168 ◽  
Author(s):  
Anthony T Reder ◽  
Kursad Genc ◽  
Paul V Byskosh ◽  
Anna Maria Porrini

Monocytes, macrophages, and microglia have a central role in the CNS inflammation of MS. Monocytes are important in the earliest events in MS. Peripheral blood monocytes secrete prostaglandins before MS attacks. During clinical activity monocyte activation markers increase and IL-1 and TNF-a levels are elevated. Other monocyte products such as IL-10 reduce inflammation. IL-10 mRNA in MNC is increased during stable disease. Manipulation of monokine secretion and expression of monocyte surface proteins are reasonable approaches for immune therapy of MS.


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