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000291762 1001_ $$0P:(DE-He78)b099c4255c1bff642f4d338ef157596e$$aHering, Marvin$$b0$$eFirst author$$udkfz
000291762 245__ $$aSphinganine recruits TLR4 adaptors in macrophages and promotes inflammation in murine models of sepsis and melanoma.
000291762 260__ $$a[London]$$bNature Publishing Group UK$$c2024
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000291762 520__ $$aAfter recognizing its ligand lipopolysaccharide, Toll-like receptor 4 (TLR4) recruits adaptor proteins to the cell membrane, thereby initiating downstream signaling and triggering inflammation. Whether this recruitment of adaptor proteins is dependent solely on protein-protein interactions is unknown. Here, we report that the sphingolipid sphinganine physically interacts with the adaptor proteins MyD88 and TIRAP and promotes MyD88 recruitment in macrophages. Myeloid cell-specific deficiency in serine palmitoyltransferase long chain base subunit 2, which encodes the key enzyme catalyzing sphingolipid biosynthesis, decreases the membrane recruitment of MyD88 and inhibits inflammatory responses in in vitro bone marrow-derived macrophage and in vivo sepsis models. In a melanoma mouse model, serine palmitoyltransferase long chain base subunit 2 deficiency decreases anti-tumor myeloid cell responses and increases tumor growth. Therefore, sphinganine biosynthesis is required for the initiation of TLR4 signal transduction and serves as a checkpoint for macrophage pattern recognition in sepsis and melanoma mouse models.
000291762 536__ $$0G:(DE-HGF)POF4-314$$a314 - Immunologie und Krebs (POF4-314)$$cPOF4-314$$fPOF IV$$x0
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000291762 650_7 $$2NLM Chemicals$$aToll-Like Receptor 4
000291762 650_7 $$2NLM Chemicals$$aMyeloid Differentiation Factor 88
000291762 650_7 $$0NGZ37HRE42$$2NLM Chemicals$$aSphingosine
000291762 650_7 $$2NLM Chemicals$$aTlr4 protein, mouse
000291762 650_7 $$0EC 2.3.1.50$$2NLM Chemicals$$aSerine C-Palmitoyltransferase
000291762 650_7 $$0OWA98U788S$$2NLM Chemicals$$asafingol
000291762 650_7 $$2NLM Chemicals$$aReceptors, Interleukin-1
000291762 650_7 $$2NLM Chemicals$$aMembrane Glycoproteins
000291762 650_7 $$2NLM Chemicals$$aMyd88 protein, mouse
000291762 650_7 $$2NLM Chemicals$$aTIRAP protein, mouse
000291762 650_7 $$2NLM Chemicals$$aTIRAP protein, human
000291762 650_7 $$2NLM Chemicals$$aLipopolysaccharides
000291762 650_2 $$2MeSH$$aAnimals
000291762 650_2 $$2MeSH$$aToll-Like Receptor 4: metabolism
000291762 650_2 $$2MeSH$$aSepsis: metabolism
000291762 650_2 $$2MeSH$$aMacrophages: metabolism
000291762 650_2 $$2MeSH$$aMyeloid Differentiation Factor 88: metabolism
000291762 650_2 $$2MeSH$$aMice
000291762 650_2 $$2MeSH$$aSphingosine: analogs & derivatives
000291762 650_2 $$2MeSH$$aSphingosine: metabolism
000291762 650_2 $$2MeSH$$aMelanoma: metabolism
000291762 650_2 $$2MeSH$$aMelanoma: pathology
000291762 650_2 $$2MeSH$$aMelanoma: genetics
000291762 650_2 $$2MeSH$$aSerine C-Palmitoyltransferase: metabolism
000291762 650_2 $$2MeSH$$aSerine C-Palmitoyltransferase: genetics
000291762 650_2 $$2MeSH$$aHumans
000291762 650_2 $$2MeSH$$aSignal Transduction
000291762 650_2 $$2MeSH$$aDisease Models, Animal
000291762 650_2 $$2MeSH$$aInflammation: metabolism
000291762 650_2 $$2MeSH$$aReceptors, Interleukin-1: metabolism
000291762 650_2 $$2MeSH$$aReceptors, Interleukin-1: genetics
000291762 650_2 $$2MeSH$$aMembrane Glycoproteins: metabolism
000291762 650_2 $$2MeSH$$aMembrane Glycoproteins: genetics
000291762 650_2 $$2MeSH$$aMice, Inbred C57BL
000291762 650_2 $$2MeSH$$aMice, Knockout
000291762 650_2 $$2MeSH$$aHEK293 Cells
000291762 650_2 $$2MeSH$$aLipopolysaccharides
000291762 7001_ $$0P:(DE-He78)f05eabc961bc296c088b3510d6429d02$$aMadi, Alaa Abdelghani Mohamed$$b1$$udkfz
000291762 7001_ $$0P:(DE-He78)a928ded2085c8911822370cad0b4a728$$aSandhoff, Roger$$b2$$udkfz
000291762 7001_ $$0P:(DE-He78)b74df323e3939b563635a2cba7a7afba$$aMa, Sicong$$b3
000291762 7001_ $$0P:(DE-He78)bf88e5f49a614f52ba8ce2cd433e6b41$$aWu, Jingxia$$b4
000291762 7001_ $$0P:(DE-He78)32b6d84a1ad5f50401b97559993ad65d$$aMieg, Alessa$$b5
000291762 7001_ $$0P:(DE-He78)027fe772631b4a2d7a45c439cdd75ff2$$aRichter, Karsten$$b6$$udkfz
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000291762 7001_ $$0P:(DE-He78)de81d854a499aca413da2a07204b2dfe$$aStichling, Diana$$b9$$udkfz
000291762 7001_ $$aPoschet, Gernot$$b10
000291762 7001_ $$0P:(DE-He78)89e155931400aa7bb80b79b6be41f979$$aBestvater, Felix$$b11$$udkfz
000291762 7001_ $$0P:(DE-He78)39a49c469ce7484849bd199f19bb1aae$$aFrank, Larissa Johanna$$b12$$udkfz
000291762 7001_ $$0P:(DE-He78)a229f7724466e7efadf4a1ace1ff8af3$$aUtikal, Jochen$$b13$$udkfz
000291762 7001_ $$0P:(DE-He78)38be34240daf8b47325afc7910e77f7b$$aUmansky, Viktor$$b14$$udkfz
000291762 7001_ $$0P:(DE-He78)0b7ce76033a6756b91f5bfb12602e20b$$aCui, Guoliang$$b15$$eLast author$$udkfz
000291762 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-024-50341-w$$gVol. 15, no. 1, p. 6067$$n1$$p6067$$tNature Communications$$v15$$x2041-1723$$y2024
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