{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:30:07Z","timestamp":1790713807237,"version":"4.1.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"7643","license":[{"start":{"date-parts":[[2017,2,22]],"date-time":"2017-02-22T00:00:00Z","timestamp":1487721600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2017,3]]},"DOI":"10.1038\/nature21368","type":"journal-article","created":{"date-parts":[[2017,2,21]],"date-time":"2017-02-21T10:42:33Z","timestamp":1487673753000},"page":"108-112","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":192,"title":["Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease"],"prefix":"10.1038","volume":"543","author":[{"given":"Manoj K.","family":"Pandey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Burrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Rani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa J.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Witte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth D.","family":"Setchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary A.","family":"Mckay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert F.","family":"Magnusen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wujuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Liou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"K\u00f6hl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Grabowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,22]]},"reference":[{"key":"BFnature21368_CR1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.ymgme.2013.09.002","volume":"111","author":"MK Pandey","year":"2014","unstructured":"Pandey, M. K. et al. Gaucher disease: chemotactic factors and immunological cell invasion in a mouse model. Mol. Genet. Metab. 111, 163\u2013171 (2014)","journal-title":"Mol. Genet. Metab."},{"key":"BFnature21368_CR2","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/1750-1172-9-51","volume":"9","author":"L van Dussen","year":"2014","unstructured":"van Dussen, L., Biegstraaten, M., Hollak, C. E. & Dijkgraaf, M. G. Cost-effectiveness of enzyme replacement therapy for type 1 Gaucher disease. Orphanet J. Rare Dis. 9, 51 (2014)","journal-title":"Orphanet J. Rare Dis."},{"key":"BFnature21368_CR3","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/acel.12409","volume":"15","author":"E Aflaki","year":"2016","unstructured":"Aflaki, E. et al. Lysosomal storage and impaired autophagy lead to inflammasome activation in Gaucher macrophages. Aging Cell 15, 77\u201388 (2016)","journal-title":"Aging Cell"},{"key":"BFnature21368_CR4","doi-asserted-by":"publisher","first-page":"e0126153","DOI":"10.1371\/journal.pone.0126153","volume":"10","author":"J Gervas-Arruga","year":"2015","unstructured":"Gervas-Arruga, J. et al. The influence of genetic variability and proinflammatory status on the development of bone disease in patients with Gaucher disease. PLoS One 10, e0126153 (2015)","journal-title":"PLoS One"},{"key":"BFnature21368_CR5","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1615\/CritRevOncog.2013006145","volume":"18","author":"PK Mistry","year":"2013","unstructured":"Mistry, P. K., Taddei, T., vom Dahl, S. & Rosenbloom, B. E. Gaucher disease and malignancy: a model for cancer pathogenesis in an inborn error of metabolism. Crit. Rev. Oncog. 18, 235\u2013246 (2013)","journal-title":"Crit. Rev. Oncog."},{"key":"BFnature21368_CR6","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s10545-010-9055-0","volume":"33","author":"G Bultron","year":"2010","unstructured":"Bultron, G. et al. The risk of Parkinson\u2019s disease in type 1 Gaucher disease. J. Inherit. Metab. Dis. 33, 167\u2013173 (2010)","journal-title":"J. Inherit. Metab. Dis."},{"key":"BFnature21368_CR7","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1016\/S0002-9440(10)63566-3","volume":"163","author":"YH Xu","year":"2003","unstructured":"Xu, Y. H., Quinn, B., Witte, D. & Grabowski, G. A. Viable mouse models of acid beta-glucosidase deficiency: the defect in Gaucher disease. Am. J. Pathol. 163, 2093\u20132101 (2003)","journal-title":"Am. J. Pathol."},{"key":"BFnature21368_CR8","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1038\/nri3761","volume":"14","author":"M Kolev","year":"2014","unstructured":"Kolev, M., Le Friec, G. & Kemper, C. Complement\u2014tapping into new sites and effector systems. Nat. Rev. Immunol. 14, 811\u2013820 (2014)","journal-title":"Nat. Rev. Immunol."},{"key":"BFnature21368_CR9","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1124\/pr.111.005223","volume":"65","author":"A Klos","year":"2013","unstructured":"Klos, A., Wende, E., Wareham, K. J. & Monk, P. N. International union of basic and clinical pharmacology. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol. Rev. 65, 500\u2013543 (2013)","journal-title":"Pharmacol. Rev."},{"key":"BFnature21368_CR10","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.immuni.2008.02.001","volume":"28","author":"MG Strainic","year":"2008","unstructured":"Strainic, M. G. et al. Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. Immunity 28, 425\u2013435 (2008)","journal-title":"Immunity"},{"key":"BFnature21368_CR11","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1002\/eji.200939333","volume":"40","author":"DJ Weaver Jr","year":"2010","unstructured":"Weaver, D. J., Jr et al. C5a receptor-deficient dendritic cells promote induction of TREG and TH17 cells. Eur. J. Immunol. 40, 710\u2013721 (2010)","journal-title":"Eur. J. Immunol."},{"key":"BFnature21368_CR12","doi-asserted-by":"publisher","first-page":"aad1210","DOI":"10.1126\/science.aad1210","volume":"352","author":"G Arbore","year":"2016","unstructured":"Arbore, G. et al. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells. Science 352, aad1210 (2016)","journal-title":"Science"},{"key":"BFnature21368_CR13","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1146\/annurev-immunol-020711-074950","volume":"31","author":"M Merad","year":"2013","unstructured":"Merad, M., Sathe, P., Helft, J., Miller, J. & Mortha, A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu. Rev. Immunol. 31, 563\u2013604 (2013)","journal-title":"Annu. Rev. Immunol."},{"key":"BFnature21368_CR14","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1074\/jbc.M310078200","volume":"279","author":"M Otto","year":"2004","unstructured":"Otto, M. et al. C5a mutants are potent antagonists of the C5a receptor (CD88) and of C5L2: position 69 is the locus that determines agonism or antagonism. J. Biol. Chem. 279, 142\u2013151 (2004)","journal-title":"J. Biol. Chem."},{"key":"BFnature21368_CR15","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1056\/NEJMoa1508808","volume":"374","author":"S Nair","year":"2016","unstructured":"Nair, S. et al. Clonal immunoglobulin against lysolipids in the origin of myeloma. N. Engl. J. Med. 374, 555\u2013561 (2016)","journal-title":"N. Engl. J. Med."},{"key":"BFnature21368_CR16","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/nri2206","volume":"8","author":"F Nimmerjahn","year":"2008","unstructured":"Nimmerjahn, F. & Ravetch, J. V. Fc\u03b3 receptors as regulators of immune responses. Nat. Rev. Immunol. 8, 34\u201347 (2008)","journal-title":"Nat. Rev. Immunol."},{"key":"BFnature21368_CR17","doi-asserted-by":"publisher","first-page":"3343","DOI":"10.1002\/eji.200939884","volume":"39","author":"SN Syed","year":"2009","unstructured":"Syed, S. N. et al. Both Fc\u03b3RIV and Fc\u03b3RIII are essential receptors mediating type II and type III autoimmune responses via FcR\u03b3-LAT-dependent generation of C5a. Eur. J. Immunol. 39, 3343\u20133356 (2009)","journal-title":"Eur. J. Immunol."},{"key":"BFnature21368_CR18","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1182\/blood-2003-05-1612","volume":"103","author":"RG Boot","year":"2004","unstructured":"Boot, R. G. et al. Marked elevation of the chemokine CCL18\/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention. Blood 103, 33\u201339 (2004)","journal-title":"Blood"},{"key":"BFnature21368_CR19","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1615\/CritRevOncog.2013004503","volume":"18","author":"MK Pandey","year":"2013","unstructured":"Pandey, M. K. & Grabowski, G. A. Immunological cells and functions in Gaucher disease. Crit. Rev. Oncog. 18, 197\u2013220 (2013)","journal-title":"Crit. Rev. Oncog."},{"key":"BFnature21368_CR20","doi-asserted-by":"publisher","first-page":"3632","DOI":"10.1093\/hmg\/dds193","volume":"21","author":"CV Cluzeau","year":"2012","unstructured":"Cluzeau, C. V. et al. Microarray expression analysis and identification of serum biomarkers for Niemann\u2013Pick disease, type C1. Hum. Mol. Genet. 21, 3632\u20133646 (2012)","journal-title":"Hum. Mol. Genet."},{"key":"BFnature21368_CR21","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/0006-291X(75)90286-7","volume":"67","author":"JN Kanfer","year":"1975","unstructured":"Kanfer, J. N., Legler, G., Sullivan, J., Raghavan, S. S. & Mumford, R. A. The Gaucher mouse. Biochem. Biophys. Res. Commun. 67, 85\u201390 (1975)","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFnature21368_CR22","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.ymgme.2012.04.020","volume":"106","author":"MK Pandey","year":"2012","unstructured":"Pandey, M. K., Rani, R., Zhang, W., Setchell, K. & Grabowski, G. A. Immunological cell type characterization and TH1\u2013TH17 cytokine production in a mouse model of Gaucher disease. Mol. Genet. Metab. 106, 310\u2013322 (2012)","journal-title":"Mol. Genet. Metab."},{"key":"BFnature21368_CR23","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.ymgme.2008.01.013","volume":"94","author":"YH Xu","year":"2008","unstructured":"Xu, Y. H. et al. Dependence of reversibility and progression of mouse neuronopathic Gaucher disease on acid \u03b2-glucosidase residual activity levels. Mol Genet. Metab. 94, 190\u2013203 (2008)","journal-title":"Mol Genet. Metab."},{"key":"BFnature21368_CR24","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen, T. D. & Livak, K. J. Analyzing real-time PCR data by the comparative CT method. Nat. Protocols 3, 1101\u20131108 (2008)","journal-title":"Nat. Protocols"},{"key":"BFnature21368_CR25","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1093\/hmg\/ddp580","volume":"19","author":"Y Sun","year":"2010","unstructured":"Sun, Y. et al. Neuronopathic Gaucher disease in the mouse: viable combined selective saposin C deficiency and mutant glucocerebrosidase (V394L) mice with glucosylsphingosine and glucosylceramide accumulation and progressive neurological deficits. Hum. Mol. Genet. 19, 1088\u20131097 (2010)","journal-title":"Hum. Mol. Genet."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature21368.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature21368","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature21368.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T13:59:29Z","timestamp":1684418369000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature21368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,22]]},"references-count":25,"journal-issue":{"issue":"7643","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["BFnature21368"],"URL":"https:\/\/doi.org\/10.1038\/nature21368","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727331215.793532832","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,22]]},"assertion":[{"value":"6 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}