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Materne, C.

Publications and source records attributed to Materne, C..

2 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↗
bioRxiv2025

REGULATION OF HDL DYSFUNCTIONALITY BY PHOSPHATIDYLETHANOLAMINE LINKS POLY-UNSATURATED FATTY ACIDS WITH ATHEROSCLEROTIC CARDIOVASCULAR DISEASES

AimsLow plasma high-density lipoprotein (HDL)-cholesterol levels are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD), potentially reflecting impaired antiatherogenic HDL functions. These latter are strongly influenced by the HDL phospholipidome, which is frequently altered in ASCVD patients. Several studies reported that plasma levels of phosphatidylethanolamine (PE) species, particularly PE (36:5), were positively associated with ASCVD, but the underlying mechanisms remain unclear. Plasma PE (36:5) exists as eicosapentaenoic (EPA)-PE and arachidonic acid (ARA)-PE, with the latter predominating in ASCVD. This study investigated whether the association of PE (36:5) with ASCVD might result from an impairment of the antiatherogenic functions of HDL. Methods and ResultsTotal PE and PE (36:5) content of large HDL isolated from 86 women with metabolic syndrome was positively associated with carotid intima-media thickness in multivariate regression analysis adjusted for traditional risk factors. In TgCETP x Ldlr-/- mice fed a high-cholesterol diet, the atherosclerotic plaque size was greater when reconstituted HDL (rHDL) containing ARA-PE was injected retro-orbitally, compared with injection of control rHDL containing only phosphatidylcholine (PC). In vitro, PE rHDL showed reduced cholesterol efflux capacity and impaired anti-inflammatory activity in THP-1 macrophages, together with diminished anti-oxidative activity against LDL oxidation compared to control rHDL. Strikingly, ARA-PE rHDL profoundly weakened of the HDL functions, while EPA-PE counteracted the ARA-PE-induced dysfunction and potentiated the functionality of rHDL. ConclusionThis study reveals a causal link between PE species, particularly ARA-PE, and HDL dysfunction, contributing to atherosclerosis. EPA-PE can restore HDL function, supporting the therapeutic potential of EPA reducing ASCVD risk.

cell biology↗