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CD14 and and TLR4 contribute to the circadian regulation of retinal phagocytosis as co-receptors
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CD14 and and TLR4 contribute to the circadian regulation of retinal phagocytosis as co-receptors
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Paper
CD14 and and TLR4 contribute to the circadian regulation of retinal phagocytosis as co-receptors
2026
Overview
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.Competing Interest StatementThe authors have declared no competing interest.Funder Information DeclaredAgence Nationale de la Recherche, ANR-17-CE14-0044-01, ANR-10-LABX-65, ANR-18-IAHU-0001Ministère de l'Enseignement Supérieur et de la Recherche, Contrat Doctoral Handicap
Publisher
Cold Spring Harbor Laboratory Press
Subject
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