Biology subjects

Gautier, E.

Publications and source records attributed to Gautier, E..

3 recordsLinked to original sources

bioRxiv2023

Obesity-elicited macrophages shape CD9hi progenitor fate to promote adipose tissue fibrosis and dysfunction

Obesity is a life-threatening condition characterized by a maladaptive remodeling of the visceral white adipose tissue (vWAT), including fibrosis, that drives vWAT metabolic alterations. We previously identified CD9hi adipose tissue progenitors as the main drivers of vWAT fibrosis in mice and humans. However, how their functions are controlled, especially by macrophages, remains largely unknown. We found that obesity-elicited monocyte-derived macrophages (obeMac) accumulation was considerably elevated in mice prone to obesity-induced vWAT fibrosis. Limiting obeMac build-up decreased the numbers and fibrogenic activation of CD9hi progenitors, leading to decreased vWAT fibrosis and improved glucose homeostasis. In patients with obesity, we identified macrophages similar to mouse obeMacs that were associated with accumulation of CD9hi progenitors in the vWAT and loss of glycemic control. Finally, intercellular communication analysis identified mediators produced by obeMacs that control the fibrogenic potential of CD9hi progenitors. Together, we uncovered an obeMac-CD9hi progenitors axis controlling vWAT fibrosis and dysfunction.

pathology↗

bioRxiv2023

Loss of embryonically-derived Kupffer cells during hypercholesterolemia accelerates atherosclerosis development

Hypercholesterolemia is a major risk factor for atherosclerosis and associated cardiovascular diseases. The liver plays a key role in the regulation of plasma cholesterol levels and hosts a large population of tissue-resident macrophages known as Kupffer cells (KCs). KCs are located in the hepatic sinusoids where they ensure key functions including blood immune surveillance. However, how KCs homeostasis is affected by the build-up of cholesterol-rich lipoproteins that occurs in the circulation during hypercholesterolemia remains unknown. Here, we found that embryo-derived KCs (EmKCs) accumulated large amounts of lipoprotein-derived cholesterol, in part through the scavenger receptor CD36, and massively expanded early after the induction of hypercholesterolemia. After this rapid adaptive response, EmKCs exhibited mitochondrial oxidative stress and their numbers gradually diminished while monocyte-derived KCs (MoKCs) with reduced cholesterol-loading capacities seeded the KC pool. Decreased proportion of EmKCs in the KC pool enhanced liver cholesterol content and exacerbated hypercholesterolemia, leading to accelerated atherosclerotic plaque development. Together, our data reveal that KC homeostasis is perturbed during hypercholesterolemia, which in turn alters the control of plasma cholesterol levels and increases atherosclerosis.

pathology↗

bioRxiv2020

Tolerogenic Dendritic Cells Shape a Transmissible Gut Microbiota that Protects from Metabolic Diseases

Excess of chronic contact between microbial motifs and intestinal immune cells are known to trigger a low-grade inflammation involved in many pathologies such as obesity and diabetes. The important skewing of intestinal adaptive immunity in the context of diet-induced obesity (DIO) is well described but how dendritic cells (DCs) participate to these changes is still poorly documented. To address this question, transgenic mice with enhanced DCs lifespan and immunogenicity (DChBcl-2 mice), are challenged with a high fat diet. Those mice display resistance to DIO and metabolic alterations. The DIO resistant phenotype is associated with healthier parameters of intestinal barrier function and lower intestinal inflammation. DChBcl-2 DIO-resistant mice demonstrate a particular increase in tolerogenic DC numbers and function which is associated with strong intestinal IgA, Th17 and T regulatory immune responses. Microbiota composition and function analyses reveal that the DChBcl-2 mice microbiota is characterized by a lower immunogenicity and an enhanced butyrate production. Cohousing experiments and fecal microbial transplantations are sufficient to transfer the DIO resistance status to WT mice demonstrating that maintenance of DCs tolerogenic ability sustains a microbiota able to drive DIO resistance. DCs tolerogenic function is revealed as a new potent target in metabolic diseases management.

immunology↗