Biology subjects

Dombrowski, Y.

Publications and source records attributed to Dombrowski, Y..

5 recordsLinked to original sources

bioRxiv2023

Regulatory T cells limit age-associated retinal inflammation and neurodegeneration

Aging is the principal risk factor for retinal degenerative diseases, which are the commonest cause of blindness in the developed countries. These conditions include age-related macular degeneration or diabetic retinopathy. Regulatory T cells play a vital role in immunoregulation of the nervous system by limiting inflammation and tissue damage in health and disease. Because the retina was long-considered an immunoprivileged site, the precise contribution of regulatory T cells in retinal homeostasis and in age-related retinal diseases remains unknown. Our study shows that regulatory T cell elimination leads to retinal pigment epithelium cell dysmorphology, and accumulation of phagocytes in the subretinal space of young and aged mice. However, only aged mice experience retinal neurodegeneration and gliosis. Surprisingly, adoptive transfer of young but not aged regulatory T cells reverse these changes. This study reveals a previously unknown protective role of regulatory T cells in maintaining aged retinal homeostasis.

neuroscience↗

bioRxiv2023

Ageing impairs the regenerative capacity of regulatory T cells in central nervous system remyelination

Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis, however, its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood. Here, we show that expansion of aged Treg does not rescue age-associated remyelination impairment due to an intrinsically diminished capacity of aged Treg to promote oligodendrocyte differentiation and myelination. This decline in regenerative Treg functions can be rescued by a young environment. We identified Melanoma Cell Adhesion Molecule 1 (MCAM1) and Integrin alpha 2 (ITGA2) as novel candidates of Treg-mediated oligodendrocyte differentiation that decrease with age. Our findings demonstrate that ageing limits the neuroregenerative capacity of Treg, likely limiting their remyelinating therapeutic potential in aged patients, and describe two novel mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation.

neuroscience↗

bioRxiv2022

E-cigarette vapour from base components propylene glycol and vegetable glycerine inhibits inflammatory response in macrophages and epithelial cells

E-cigarettes are a highly popular nicotine replacement therapy in the process of smoking cessation. Despite this, research on the effects of E-vapours to human health remains limited. The popularity of vaping and mass production of cheap E-liquids has led to compromised safety regulations, with contaminants such as heavy metals and alkaloids detected in multiple liquids. Vaporised E-liquids increase cellular ROS generation and inflammatory cytokine release from pulmonary macrophages. This suggests that E-cigarette usage might activate inflammasomes. Common food additives vegetable glycerine (VG) and propylene glycol (PG) form the base of all E-liquids, but little is known about their inflammatory potential once inhaled. Here, the effect of base components PG and VG on inflammasome activation and cytokine release was investigated in macrophages and epithelial cells exposed to E-liquids and vaporised E-liquid extract (E-vapour). Base E-liquid and E-vapour did not induce cellular cytotoxicity and non-vapourised E-liquid had no effect on IL-8 release. However, basic PG/VG E-vapour inhibited both IL-8 release and conventional inflammasome activation by known inflammatory activators in macrophages and epithelial cells. These results propose a novel inhibitory effect of basic E-vapour components to inflammatory challenges.

immunology↗

bioRxiv2019

The microbiota regulates inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination

The microbiota is now recognised as a key influence on the host immune response in the central nervous system (CNS). As such, there has been some progress towards therapies that modulate the microbiota with the aim of limiting immune-mediated demyelination, as occurs in multiple sclerosis. However, remyelination - the regeneration of myelin sheaths - also depends upon an immune response, and the effects that such interventions might have on remyelination have not yet been explored. Here, we show that the inflammatory response during CNS remyelination in mice is modulated by antibiotic or probiotic treatment, as well as in germ-free mice. We also explore the effect of these changes on oligodendrocyte progenitor cell differentiation, which is inhibited by antibiotics but unaffected by our other interventions. These results reveal that high combined doses of oral antibiotics negatively influence remyelination and further our understanding of how mammalian regeneration relates to the microbiota.

neuroscience↗

bioRxiv2017

QuPath: Open source software for digital pathology image analysis

QuPath is new bioimage analysis software designed to meet the growing need for a user-friendly, extensible, open-source solution for digital pathology and whole slide image analysis. In addition to offering a comprehensive panel of tumor identification and high-throughput biomarker evaluation tools, QuPath provides researchers with powerful batch-processing and scripting functionality, and an extensible platform with which to develop and share new algorithms to analyze complex tissue images. Furthermore, QuPaths flexible design make it suitable for a wide range of additional image analysis applications across biomedical research.

pathology↗