Biology subjects

Dubourdeau, M.

Publications and source records attributed to Dubourdeau, M..

3 recordsLinked to original sources

bioRxiv2025

Lymphangiogenesis in Abdominal Aortic Aneurysm regulates the balance between resident and circulating eosinophils via a 15-lipoxygenase-dependent mechanism

The abdominal aortic aneurysm (AAA) is a chronic degeneration of the aortic wall involving an inflammatory response, aberrant remodeling of the extracellular matrix, and the development of microvessels. Among these, lymphatic capillaries develop in the adventitia. However, the role of lymphangiogenesis in AAA remains unclear. Here, we confirmed the development of lymphatic vessels in both human and mouse AAA. This was associated with a decrease in specialized pro-resolving mediators (SPM) generated by 15-Lipoxygenase (15LO), an enzyme that controls resolution of inflammation in lymphatic diseases. Lymphatic selective depletion of 15LO (Prox1cre; Alox15fl/fl mice) increased both systemic and resident eosinophil (EOS) accumulation in lesions, but had no effect on other immune cell populations. Mechanistically, in vitro depletion of 15LO in lymphatic endothelial cells (LEC) significantly decreased EOS adhesion. In contrast, 15LO LEC depletion improved transendothelial migration. In vivo, the rescue of 15LO using lentivector transduction modified the balance between resident and systemic EOS in favor of the resident ones and reduced the AAA lesion. Altogether, we show that lymphatic vessels play a protective role in AAA by regulating the trafficking of EOS into the aorta wall.

cell biology↗

bioRxiv2024

Polyunsaturated fatty acid-derived lipid mediator networks characterize COVID-19 severity and risk for critical illness

Severe COVID-19, caused by SARS-CoV-2 infection, is characterized by excessive inflammation leading to the development of pneumonia and acute respiratory distress syndrome. Bioactive lipid mediators (LMs) derived from {omega}6 and {omega}3 polyunsaturated fatty acids are central to the regulation of inflammation, controlling both its initiation and resolution. Still, their role in COVID-19 remains underexplored. By employing a holistic approach involving the analysis of white blood cell transcriptomes, targeted lipidomics, cytokine and immune cell profiling, across the spectrum of disease severity groups, including mild non-hospitalized patients and healthy individuals, we now show that LM networks are profoundly altered in COVID-19, correlate with inflammatory patterns, and stratify patients according to disease severity. Central to this are CYP450-derived LMs such as 20-HETE, lipid peroxidation metabolites such as iPF2a-VI, and lipoxygenase-derived LMs such as 12-HETE, all of which are major vasoactive mediators of inflammation. Among them, 20-HETE appears to be a promising prognostic biomarker for ICU admission and a potential therapeutic target for severe COVID-19 disease. Our study thus underscores the significance of LM networks in COVID-19 pathophysiology and sheds light into the broader mechanisms driving viral pneumonia in humans. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/610123v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@6e406dorg.highwire.dtl.DTLVardef@47c9deorg.highwire.dtl.DTLVardef@1162488org.highwire.dtl.DTLVardef@b86ba3_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

The Atlas of Inflammation-Resolution (AIR)

Acute inflammation is a protective reaction by the immune system in response to invading pathogens or tissue damage. Ideally, the response should be localized, self-limited, and returning to homeostasis. If not resolved, acute inflammation can result in organ pathologies leading to chronic inflammatory phenotypes. Acute inflammation and inflammation resolution are complex coordinated processes, involving a number of cell types, interacting in space and time. The biomolecular complexity and the fact that several biomedical fields are involved, make a multi and interdisciplinary approach necessary. This Atlas of Inflammation Resolution (AIR) is a web-based resource capturing the state-of-the-art in acute inflammation and inflammation resolution research. The AIR provides an interface for users to search thousands of interactions, arranged in inter-connected multi-layers of process diagrams, covering a wide range of clinically relevant phenotypes. The AIR serves as an open access knowledgebase, including a gateway to numerous public databases. It is furthermore possible for the user to map experimental data onto the molecular interaction maps of the AIR, providing the basis for bioinformatics analyses and systems biology approaches. By mapping experimental data onto the Atlas, it can be used to elucidate drug action as well as molecular mechanisms underlying different disease phenotypes. For the visualization and exploration of information, the AIR uses the Minerva platform, which is a well-established tool for the presentation of disease maps. The molecular details of the AIR are encoded using international standards. The Atlas of Inflammation Resolution was created as a freely accessible resource, supporting research and education in the fields of acute inflammation and inflammation resolution. The AIR connects research communities, facilitates clinical decision making, and supports research scientists in the formulation and validation of hypotheses.

immunology↗