Biology subjects

Marcelin, G.

Publications and source records attributed to Marcelin, G..

3 recordsLinked to original sources

bioRxiv2026

CD14 and and TLR4 contribute to the circadian regulation of retinal phagocytosis as co-receptors

Retinal pigment epithelium (RPE) cells perform crucial functions for vision, among which the daily clearance of photoreceptor outer segment (POS) oxidized extremities. POS phagocytosis is under circadian regulation, peaking only once a day despite the constant contact between both cell types. Alphavbeta5 integrin receptors and MFG-E8 ligands synchronize POS phagocytosis and activate the MerTK internalization receptor via an intracellular signaling cascade. Recently, we identified scavenger receptors CD36 and SR-B2/LIMP2 as POS internalization regulators. We now highlight that innate immunity receptors CD14 and TLR4 interact with POS as stimulatory coreceptors in a tissue-specific fashion. CD14 and TLR4 associate partially with lipid rafts, and their activation triggers MyD88-dependent JNK and ERK1/2 (p44/42) kinases. In vivo, CD14 and TLR4 protein levels are replenished in the hours leading to the phagocytic peak. In addition, the phagocytic peak is lost in Tlr4-/- RPE cells, thus confirming that TLR4 regulates this function. Finally, CD14 and TLR4 associate with SR-B2, partner with CD36 and MerTK, highlighting that several receptors contribute together to the fine regulation of POS phagocytosis as a macromolecular machinery.

cell biology↗

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

Dietary fibers benefits on glucose homeostasis require type 2 conventional dendritic cells in mice fed a high-fat diet

Diet composition impacts metabolic health and is now recognized to shape the immune system, especially in the intestinal tract. Nutritional imbalance and increased caloric intake are induced by high-fat diet (HFD) in which lipids are enriched at the expense of dietary fibers. Such nutritional challenge alters glucose homeostasis as well as intestinal immunity. Here, we observed that short-term HFD induced dysbiosis, glucose intolerance and decreased intestinal ROR{gamma}t+ CD4 T cells, including peripherally-induced Tregs and IL17-producing (Th17) T cells. However, dietary fiber supplementation of HFD-fed animals was sufficient to maintain ROR{gamma}t+ CD4 T cell subsets and microbial species known to induce them, alongside having a beneficial impact on glucose tolerance. Dietary fiber-mediated normalization of Th17 cells and amelioration of glucose handling required the cDC2 dendritic cell subset in HFD-fed animals, while IL-17 neutralization limited fibers impact on glucose tolerance. Overall, we uncover a novel and pivotal role of cDC2 in the control of the immune and metabolic effects of dietary fibers in the context of HFD feeding.

immunology↗