000268464 001__ 268464 000268464 005__ 20240317002755.0 000268464 0247_ $$2doi$$a10.1126/sciimmunol.adi9769 000268464 0247_ $$2pmid$$apmid:38207055 000268464 0247_ $$2altmetric$$aaltmetric:158298957 000268464 037__ $$aDZNE-2024-00216 000268464 041__ $$aEnglish 000268464 082__ $$a610 000268464 1001_ $$00000-0002-9092-1684$$aWolf, Christine$$b0 000268464 245__ $$aUNC93B1 variants underlie TLR7-dependent autoimmunity. 000268464 260__ $$aWashington, DC$$bAAAS$$c2024 000268464 3367_ $$2DRIVER$$aarticle 000268464 3367_ $$2DataCite$$aOutput Types/Journal article 000268464 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1710238325_4388 000268464 3367_ $$2BibTeX$$aARTICLE 000268464 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000268464 3367_ $$00$$2EndNote$$aJournal Article 000268464 520__ $$aUNC93B1 is critical for trafficking and function of nucleic acid-sensing Toll-like receptors (TLRs) TLR3, TLR7, TLR8, and TLR9, which are essential for antiviral immunity. Overactive TLR7 signaling induced by recognition of self-nucleic acids has been implicated in systemic lupus erythematosus (SLE). Here, we report UNC93B1 variants (E92G and R336L) in four patients with early-onset SLE. Patient cells or mouse macrophages carrying the UNC93B1 variants produced high amounts of TNF-α and IL-6 and upon stimulation with TLR7/TLR8 agonist, but not with TLR3 or TLR9 agonists. E92G causes UNC93B1 protein instability and reduced interaction with TLR7, leading to selective TLR7 hyperactivation with constitutive type I IFN signaling. Thus, UNC93B1 regulates TLR subtype-specific mechanisms of ligand recognition. Our findings establish a pivotal role for UNC93B1 in TLR7-dependent autoimmunity and highlight the therapeutic potential of targeting TLR7 in SLE. 000268464 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x0 000268464 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000268464 650_7 $$2NLM Chemicals$$aToll-Like Receptor 7 000268464 650_7 $$2NLM Chemicals$$aToll-Like Receptor 9 000268464 650_7 $$2NLM Chemicals$$aToll-Like Receptor 8 000268464 650_7 $$2NLM Chemicals$$aToll-Like Receptor 3 000268464 650_7 $$2NLM Chemicals$$aTLR7 protein, human 000268464 650_7 $$2NLM Chemicals$$aUNC93B1 protein, human 000268464 650_7 $$2NLM Chemicals$$aMembrane Transport Proteins 000268464 650_7 $$2NLM Chemicals$$aUNC93B1 protein, mouse 000268464 650_2 $$2MeSH$$aMice 000268464 650_2 $$2MeSH$$aAnimals 000268464 650_2 $$2MeSH$$aHumans 000268464 650_2 $$2MeSH$$aToll-Like Receptor 7: genetics 000268464 650_2 $$2MeSH$$aAutoimmunity: genetics 000268464 650_2 $$2MeSH$$aToll-Like Receptor 9: metabolism 000268464 650_2 $$2MeSH$$aToll-Like Receptor 8 000268464 650_2 $$2MeSH$$aToll-Like Receptor 3: metabolism 000268464 650_2 $$2MeSH$$aLupus Erythematosus, Systemic: genetics 000268464 650_2 $$2MeSH$$aMembrane Transport Proteins 000268464 7001_ $$00000-0002-5173-2979$$aLim, Ee Lyn$$b1 000268464 7001_ $$00000-0003-0658-2147$$aMokhtari, Mohammad$$b2 000268464 7001_ $$00009-0002-5254-6411$$aKind, Barbara$$b3 000268464 7001_ $$00000-0002-2806-6904$$aOdainic, Alexandru$$b4 000268464 7001_ $$aLara-Villacanas, Eusebia$$b5 000268464 7001_ $$aKoss, Sarah$$b6 000268464 7001_ $$00000-0003-1447-6811$$aMages, Simon$$b7 000268464 7001_ $$00009-0001-8558-3692$$aMenzel, Katharina$$b8 000268464 7001_ $$aEngel, Kerstin$$b9 000268464 7001_ $$aDückers, Gregor$$b10 000268464 7001_ $$aBernbeck, Benedikt$$b11 000268464 7001_ $$00000-0001-8153-1601$$aSchneider, Dominik T$$b12 000268464 7001_ $$aSiepermann, Kathrin$$b13 000268464 7001_ $$00000-0002-9945-8833$$aNiehues, Tim$$b14 000268464 7001_ $$00000-0003-3407-7631$$aGoetzke, Carl Christoph$$b15 000268464 7001_ $$00000-0002-6179-0670$$aDurek, Pawel$$b16 000268464 7001_ $$aMinden, Kirsten$$b17 000268464 7001_ $$00000-0002-6478-7725$$aDörner, Thomas$$b18 000268464 7001_ $$00000-0002-0500-0304$$aStittrich, Anna$$b19 000268464 7001_ $$00000-0001-7850-5971$$aSzelinski, Franziska$$b20 000268464 7001_ $$00000-0002-9773-4929$$aGuerra, Gabriela Maria$$b21 000268464 7001_ $$aMassoud, Mona$$b22 000268464 7001_ $$00000-0002-5561-3635$$aBieringer, Markus$$b23 000268464 7001_ $$00000-0002-1852-9880$$ade Oliveira Mann, Carina C$$b24 000268464 7001_ $$00000-0002-7266-4098$$aBeltrán, Eduardo$$b25 000268464 7001_ $$00000-0003-2404-9397$$aKallinich, Tilmann$$b26 000268464 7001_ $$00000-0002-8015-6907$$aMashreghi, Mir-Farzin$$b27 000268464 7001_ $$00000-0001-9561-2752$$aSchmidt, Susanne V$$b28 000268464 7001_ $$0P:(DE-2719)2000062$$aLatz, Eicke$$b29$$udzne 000268464 7001_ $$00000-0002-3628-9278$$aKlughammer, Johanna$$b30 000268464 7001_ $$00000-0001-9467-4898$$aMajer, Olivia$$b31 000268464 7001_ $$00000-0002-4008-9869$$aLee-Kirsch, Min Ae$$b32 000268464 773__ $$0PERI:(DE-600)2862556-0$$a10.1126/sciimmunol.adi9769$$gVol. 9, no. 92, p. eadi9769$$n92$$peadi9769$$tScience immunology$$v9$$x2470-9468$$y2024 000268464 8564_ $$uhttps://pub.dzne.de/record/268464/files/DZNE-2024-00216_Restricted.pdf 000268464 8564_ $$uhttps://pub.dzne.de/record/268464/files/DZNE-2024-00216_Restricted.pdf?subformat=pdfa$$xpdfa 000268464 909CO $$ooai:pub.dzne.de:268464$$pVDB 000268464 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000062$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b29$$kDZNE 000268464 9131_ $$0G:(DE-HGF)POF4-351$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vBrain Function$$x0 000268464 9141_ $$y2024 000268464 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bSCI IMMUNOL : 2022$$d2023-08-23 000268464 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-23 000268464 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-23 000268464 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-23 000268464 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-08-23 000268464 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-08-23 000268464 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-23 000268464 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-08-23 000268464 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-08-23 000268464 915__ $$0StatID:(DE-HGF)9920$$2StatID$$aIF >= 20$$bSCI IMMUNOL : 2022$$d2023-08-23 000268464 9201_ $$0I:(DE-2719)1013024$$kAG Latz ; 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