Cantuti-Castelvetri, Ludovico

[["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Journal of Experimental Medicine"],["dc.bibliographiccitation.volume","218"],["dc.contributor.author","Gouna, Garyfallia"],["dc.contributor.author","Klose, Christian"],["dc.contributor.author","Bosch-Queralt, Mar"],["dc.contributor.author","Liu, Lu"],["dc.contributor.author","Gokce, Ozgun"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Cantuti-Castelvetri, Ludovico"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2022-08-19T07:04:48Z"],["dc.date.available","2022-08-19T07:04:48Z"],["dc.date.issued","2021"],["dc.description.abstract","Upon demyelinating injury, microglia orchestrate a regenerative response that promotes myelin repair, thereby restoring rapid signal propagation and protecting axons from further damage. Whereas the essential phagocytic function of microglia for remyelination is well known, the underlying metabolic pathways required for myelin debris clearance are poorly understood. Here, we show that cholesterol esterification in male mouse microglia/macrophages is a necessary adaptive response to myelin debris uptake and required for the generation of lipid droplets upon demyelinating injury. When lipid droplet biogenesis is defective, innate immune cells do not resolve, and the regenerative response fails. We found that triggering receptor expressed on myeloid cells 2 (TREM2)-deficient mice are unable to adapt to excess cholesterol exposure, form fewer lipid droplets, and build up endoplasmic reticulum (ER) stress. Alleviating ER stress in TREM2-deficient mice restores lipid droplet biogenesis and resolves the innate immune response. Thus, we conclude that TREM2-dependent formation of lipid droplets constitute a protective response required for remyelination to occur."],["dc.identifier.doi","10.1084/jem.20210227"],["dc.identifier.pmid","34424266"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113016"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/41"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation.eissn","1540-9538"],["dc.relation.issn","0022-1007"],["dc.relation.workinggroup","RG Cantuti"],["dc.relation.workinggroup","RG Gokce (Systems Neuroscience – Cell Diversity)"],["dc.relation.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","109898"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Penkert, Horst"],["dc.contributor.author","Bertrand, Alix"],["dc.contributor.author","Tiwari, Vini"],["dc.contributor.author","Breimann, Stephan"],["dc.contributor.author","Müller, Stephan A."],["dc.contributor.author","Jordan, Paul M."],["dc.contributor.author","Gerl, Mathias J."],["dc.contributor.author","Klose, Christian"],["dc.contributor.author","Cantuti-Castelvetri, Ludovico"],["dc.contributor.author","Bosch-Queralt, Mar"],["dc.contributor.author","Levental, Ilya"],["dc.contributor.author","Lichtenthaler, Stefan F."],["dc.contributor.author","Werz, Oliver"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2022-08-19T07:10:22Z"],["dc.date.available","2022-08-19T07:10:22Z"],["dc.date.issued","2021"],["dc.description.abstract","After demyelinating injury of the central nervous system, resolution of the mounting acute inflammation is crucial for the initiation of a regenerative response. Here, we aim to identify fatty acids and lipid mediators that govern the balance of inflammatory reactions within demyelinating lesions. Using lipidomics, we identify bioactive lipids in the resolution phase of inflammation with markedly elevated levels of n-3 polyunsaturated fatty acids. Using fat-1 transgenic mice, which convert n-6 fatty acids to n-3 fatty acids, we find that reduction of the n-6/n-3 ratio decreases the phagocytic infiltrate. In addition, we observe accelerated decline of microglia/macrophages and enhanced generation of oligodendrocytes in aged mice when n-3 fatty acids are shuttled to the brain. Thus, n-3 fatty acids enhance lesion recovery and may, therefore, provide the basis for pro-regenerative medicines of demyelinating diseases in the central nervous system."],["dc.identifier.doi","10.1016/j.celrep.2021.109898"],["dc.identifier.pmid","34706241"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113018"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/45"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation.eissn","2211-1247"],["dc.relation.workinggroup","RG Cantuti"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","Proteomic and lipidomic profiling of demyelinating lesions identifies fatty acids as modulators in lesion recovery"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","211"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Nature Metabolism"],["dc.bibliographiccitation.lastpage","227"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Bosch-Queralt, Mar"],["dc.contributor.author","Cantuti-Castelvetri, Ludovico"],["dc.contributor.author","Damkou, Alkmini"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Schlepckow, Kai"],["dc.contributor.author","Alexopoulos, Ioannis"],["dc.contributor.author","Lütjohann, Dieter"],["dc.contributor.author","Klose, Christian"],["dc.contributor.author","Vaculčiaková, Lenka"],["dc.contributor.author","Masuda, Takahiro"],["dc.contributor.author","Prinz, Marco"],["dc.contributor.author","Monroe, Kathryn M."],["dc.contributor.author","Di Paolo, Gilbert"],["dc.contributor.author","Lewcock, Joseph W."],["dc.contributor.author","Haass, Christian"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2022-08-18T14:19:20Z"],["dc.date.available","2022-08-18T14:19:20Z"],["dc.date.issued","2021"],["dc.description.abstract","Proregenerative responses are required for the restoration of nervous-system functionality in demyelinating diseases such as multiple sclerosis (MS). Yet, the limiting factors responsible for poor CNS repair are only partially understood. Here, we test the impact of a Western diet (WD) on phagocyte function in a mouse model of demyelinating injury that requires microglial innate immune function for a regenerative response to occur. We find that WD feeding triggers an ageing-related, dysfunctional metabolic response that is associated with impaired myelin-debris clearance in microglia, thereby impairing lesion recovery after demyelination. Mechanistically, we detect enhanced transforming growth factor beta (TGFβ) signalling, which suppresses the activation of the liver X receptor (LXR)-regulated genes involved in cholesterol efflux, thereby inhibiting phagocytic clearance of myelin and cholesterol. Blocking TGFβ or promoting triggering receptor expressed on myeloid cells 2 (TREM2) activity restores microglia responsiveness and myelin-debris clearance after demyelinating injury. Thus, we have identified a druggable microglial immune checkpoint mechanism regulating the microglial response to injury that promotes remyelination."],["dc.identifier.doi","10.1038/s42255-021-00341-7"],["dc.identifier.pmid","33619376"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113011"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/25"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation.issn","2522-5812"],["dc.relation.workinggroup","RG Cantuti"],["dc.relation.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","Diet-dependent regulation of TGFβ impairs reparative innate immune responses after demyelination"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]