Immune response of BV-2 microglial cells is impacted by peroxisomal beta-oxidation

Microglia are crucial for brain homeostasis, and dysfunction of these cells is a key driver in most neurodegenerative diseases, including peroxisomal leukodystrophies. In X-linked adrenoleukodystrophy (X-ALD), a neuroinflammatory disorder, very long-chain fatty acid (VLCFA) accumulation due to impaired degradation within peroxisomes results in microglial defects, but the underlying mechanisms remain unclear. Using CRISPR/Cas9 gene editing of key genes in peroxisomal VLCFA breakdown (Abcd1, Abcd2, and Acox1), we recently established easily accessible microglial BV-2 cell models to study the impact of dysfunctional peroxisomal β-oxidation and revealed a disease-associated microglial-like signature in these cell lines. Transcriptomic analysis suggested consequences on the immune response. To clarify how impaired lipid degradation impacts the immune function of microglia, we here used RNA-sequencing and functional assays related to the immune response to compare wild-type and mutant BV-2 cell lines under basal conditions and upon pro-inflammatory lipopolysaccharide (LPS) activation. A majority of genes encoding proinflammatory cytokines, as well as genes involved in phagocytosis, antigen presentation, and co-stimulation of T lymphocytes, were found differentially overexpressed. The transcriptomic alterations were reflected by altered phagocytic capacity, inflammasome activation, increased release of inflammatory cytokines, including TNF, and upregulated response of T lymphocytes primed by mutant BV-2 cells presenting peptides. Together, the present study shows that peroxisomal β-oxidation defects resulting in lipid alterations, including VLCFA accumulation, directly reprogram the main cellular functions of microglia. The elucidation of this link between lipid metabolism and the immune response of microglia will help to better understand the pathogenesis of peroxisomal leukodystrophies

TOLERANCE DES IMMUNOGLOBULINES (PRISE EN COMPTE POUR UNE PROPOSITION DE DEMARCHE QUALITE (DES PHARMACIE SPECIALISEE))

BESANCON-BU Médecine pharmacie (250562102) / SudocSudocFranceF

Landscape restauration in the Amazon: land suitability and jurisdictional governance to achieve ecologic and economics goals. [ID843]

In the Amazonian “arc of deforestation”, landscapes are a result of 50 years of systematic deforestations, driven by a "race to the land", where land appropriation was the main objective of the migrants. In this context, land accumulation was a priority over land production, and even more over sustainable management of natural resources. In consequence, current landscapes include huge areas of systematic deforestation, and disconnected forest remaining patches. Both are degraded. Agronomic productivities are decreasing, due to extractive management systems. Ecosystemic services also are low, due to forest fragmentation, soil degradation and deforestation of vulnerable areas. Since 2005 - 2008, federal policies against deforestation and forest act have fixed the usable agricultural areas, and economic growth must now take place in a limited land extension. Natural resources management becomes essential, which induces changes in farming practices. In this transition, land suitability becomes a key to organize a new farming design, zoning areas dedicated to economic production, and areas for ecosystemic services. In the first ones, improved and intensified agricultural practices are developed, valorizing best soils and or topographic units. The other areas, less productive but with a high connectivity and potentiality for water cycle and soil protection, are abounded and could go back to forest regeneration. A new forest matrix is being built, as well as a new map of agricultural production. Landscape efficiency is also defined by the optimized combination of these two maps. Land suitability defines the tradeoff between economic production and ecosystemic services. This presentation explains the Paragominas experience, in Brazilian eastern amazon, to develop a landscape restoration plan, in a jurisdictional approach. In a first step, land suitability is mapped at municipal level, using topographic data, and derived information's about soils, declivity and hydrographic network. All categories are related to farmer's practices, and discussed with them. In a second step, land uses are also mapped, especially forest cover and forest degradation, using middle resolution remote sensing data. In the third step, land uses and suitability's are spatially crossed in a GIS, in order to define strategic areas for ecosystemic services by reforestation or forest restauration, and other strategic areas for economic production, by improved practices (especially tree-crop-livestock integration). In a fourth step, this cartography become a municipal law for land use, discussed and voted in the municipal congress. In a fifth step, every farmer can develop a new farming design, according to this mapping, and possibly accessing a specific credit line and facilities. By this way, forest restoration is growing, especially in the strategic areas, and with a higher connectivity index. It is possible to improve ecosystemic services, above the Brazilian NDC in COP 21 for example, not only for carbon sequestration but also for water cycle, soil protection and biodiversity. This win-win strategy, based on land suitability, is attractive for farmers and all private sector, and also can achieve higher results than only command and control policies. In the other hand, it needs a strong monitoring capacity in the jurisdiction, and good governance mechanisms

Landscape restoration in the Amazon: land suitability and jurisdictional governance to achieve ecologic and economics goals

International audienc