{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:56:39Z","timestamp":1791226599544,"version":"4.1.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"6911","license":[{"start":{"date-parts":[[2002,11,1]],"date-time":"2002-11-01T00:00:00Z","timestamp":1036108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2002,11]]},"DOI":"10.1038\/nature01158","type":"journal-article","created":{"date-parts":[[2002,11,6]],"date-time":"2002-11-06T19:46:20Z","timestamp":1036611980000},"page":"78-84","source":"Crossref","is-referenced-by-count":906,"title":["The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease"],"prefix":"10.1038","volume":"420","author":[{"given":"Sawsan","family":"Youssef","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"St\u00fcve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Patarroyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro J.","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Radosevich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Mi","family":"Hur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Bravo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis J.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond A.","family":"Sobel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Steinman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott S.","family":"Zamvil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"BFnature01158_CR1","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1056\/NEJM199509073331003","volume":"333","author":"JA Kobashigawa","year":"1995","unstructured":"Kobashigawa, J. A. et al. Effect of pravastatin on outcomes after cardiac transplantation. N. Engl. J. Med. 333, 621\u2013627 (1995)","journal-title":"N. Engl. J. Med."},{"key":"BFnature01158_CR2","doi-asserted-by":"publisher","first-page":"2671","DOI":"10.1172\/JCI119812","volume":"100","author":"K Pahan","year":"1997","unstructured":"Pahan, K., Sheikh, F. G., Namboodiri, A. M. & Singh, I. Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. J. Clin. Invest. 100, 2671\u20132679 (1997)","journal-title":"J. Clin. Invest."},{"key":"BFnature01158_CR3","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1189\/jlb.69.6.959","volume":"69","author":"B Wong","year":"2001","unstructured":"Wong, B. et al. Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation. J. Leukoc. Biol. 69, 959\u2013962 (2001)","journal-title":"J. Leukoc. Biol."},{"key":"BFnature01158_CR4","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1146\/annurev.iy.08.040190.003051","volume":"8","author":"SS Zamvil","year":"1990","unstructured":"Zamvil, S. S. & Steinman, L. The T lymphocyte in experimental allergic encephalomyelitis. Annu. Rev. Immunol. 8, 579\u2013621 (1990)","journal-title":"Annu. Rev. Immunol."},{"key":"BFnature01158_CR5","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1172\/JCI13360","volume":"108","author":"AJ Slavin","year":"2001","unstructured":"Slavin, A. J. et al. Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity. J. Clin. Invest. 108, 1133\u20131139 (2001)","journal-title":"J. Clin. Invest."},{"key":"BFnature01158_CR6","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1038\/labinvest.3780115","volume":"80","author":"M Romano","year":"2000","unstructured":"Romano, M. et al. Inhibition of monocyte chemotactic protein-1 synthesis by statins. Lab. Invest. 80, 1095\u20131100 (2000)","journal-title":"Lab. Invest."},{"key":"BFnature01158_CR7","doi-asserted-by":"publisher","first-page":"7111","DOI":"10.1073\/pnas.78.11.7111","volume":"78","author":"L Steinman","year":"1981","unstructured":"Steinman, L., Rosenbaum, J. T., Sriram, S. & McDevitt, H. O. In vivo effects of antibodies to immune response gene products: prevention of experimental allergic encephalomyelitis. Proc. Natl Acad. Sci. USA 78, 7111\u20137114 (1981)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature01158_CR8","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/S0140-6736(83)90629-3","volume":"2","author":"GF Bottazo","year":"1983","unstructured":"Bottazo, G. F., Pujol-Borrell, R., Hanufusa, T. & Feldmann, M. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet 2, 1115\u20131119 (1983)","journal-title":"Lancet"},{"key":"BFnature01158_CR9","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1038\/82219","volume":"6","author":"B Kwak","year":"2000","unstructured":"Kwak, B., Mulhaupt, F., Myit, S. & Mach, F. Statins as a newly recognized type of immunomodulator. Nature Med. 6, 1399\u20131402 (2000)","journal-title":"Nature Med."},{"key":"BFnature01158_CR10","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1146\/annurev.immunol.14.1.301","volume":"14","author":"B Mach","year":"1996","unstructured":"Mach, B., Steimle, V., Martinez-Soria, E. & Reith, W. Regulation of MHC class II genes: lessons from a disease. Annu. Rev. Immunol. 14, 301\u2013331 (1996)","journal-title":"Annu. Rev. Immunol."},{"key":"BFnature01158_CR11","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1093\/emboj\/16.10.2851","volume":"16","author":"A Muhlethaler-Mottet","year":"1997","unstructured":"Muhlethaler-Mottet, A., Otten, L. A., Steimle, V. & Mach, B. Expression of MHC class II molecules in different cellular and functional compartments is controlled by differential usage of multiple promoters of the transactivator CIITA. EMBO J. 16, 2851\u20132860 (1997)","journal-title":"EMBO J."},{"key":"BFnature01158_CR12","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1097\/00005072-199603000-00005","volume":"55","author":"A Maeda","year":"1996","unstructured":"Maeda, A. & Sobel, R. A. Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. 55, 300\u2013309 (1996)","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"BFnature01158_CR13","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1097\/00041327-200112000-00012","volume":"21","author":"RA Rudick","year":"2001","unstructured":"Rudick, R. A. Contemporary immunomodulatory therapy for multiple sclerosis. J. Neuroophthalmol. 21, 284\u2013291 (2001)","journal-title":"J. Neuroophthalmol."},{"key":"BFnature01158_CR14","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1056\/NEJM200202143460721","volume":"346","author":"JA Staffa","year":"2002","unstructured":"Staffa, J. A., Chang, J. & Green, L. Cerivastatin and reports of fatal rhabdomyolysis. N. Engl. Med. 346, 539\u2013540 (2002)","journal-title":"N. Engl. Med."},{"key":"BFnature01158_CR15","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1023\/A:1011908004965","volume":"15","author":"F Bernini","year":"2001","unstructured":"Bernini, F., Poli, A. & Paoletti, R. Safety of HMG-CoA reductase inhibitors: focus on atorvastatin. Cardiovasc. Drugs Ther. 15, 211\u2013218 (2001)","journal-title":"Cardiovasc. Drugs Ther."},{"key":"BFnature01158_CR16","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/S0009-9236(96)90218-0","volume":"60","author":"DD Cilla Jr","year":"1996","unstructured":"Cilla, D. D. Jr, Whitfield, L. R., Gibson, D. M., Sedman, A. J. & Posvar, E. L. Multiple-dose pharmacokinetics, pharmacodynamics, and safety and atorvastatin, an inhibitor of HMG-CoA reductase, in healthy subjects. Clin. Pharmacol. Ther. 60, 687\u2013695 (1996)","journal-title":"Clin. Pharmacol. Ther."},{"key":"BFnature01158_CR17","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1006\/faat.1996.0132","volume":"32","author":"LA Dostal","year":"1996","unstructured":"Dostal, L. A., Whitfield, I. R. & Anderson, J. A. Fertility and general reproduction studies in rats with the HMG-CoA reductase inhibitor, atorvastatin. Fundam. Appl. Toxicol. 32, 285\u2013292 (1996)","journal-title":"Fundam. Appl. Toxicol."},{"key":"BFnature01158_CR18","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1073\/pnas.92.2.354","volume":"92","author":"F Hardardottir","year":"1995","unstructured":"Hardardottir, F., Baron, J. L. & Janeway, C. A. Jr. T cells with two functional antigen-specific receptors. Proc. Natl Acad. Sci. USA 92, 354\u2013358 (1995)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature01158_CR19","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1128\/MCB.19.1.431","volume":"19","author":"JF Piskurich","year":"1999","unstructured":"Piskurich, J. F., Linhoff, M. W., Wang, Y. & Ting, J. P. Y. Two distinct gamma interferon-inducible promoters of the major histocompatibility complex class II transactivator gene are differentially regulated by STAT1, interferon regulatory factor 1, and transforming growth factor beta. Mol. Cell. Biol. 19, 431\u2013440 (1999)","journal-title":"Mol. Cell. Biol."},{"key":"BFnature01158_CR20","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1084\/jem.194.4.393","volume":"194","author":"JM Waldburger","year":"2001","unstructured":"Waldburger, J. M., Suter, T., Fontana, A., Acha-Orbea, H. & Reith, W. Selective abrogation of major histocompatibility complex class II expression on extrahematopoietic cells in mice lacking promoter IV of the class II transactivator gene. J. Exp. Med. 194, 393\u2013406 (2001)","journal-title":"J. Exp. Med."},{"key":"BFnature01158_CR21","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1002\/glia.1125","volume":"36","author":"JM Soos","year":"2001","unstructured":"Soos, J. M. et al. Malignant glioma cells use MHC class II transactivator (CIITA) promoters III and IV to direct IFN-gamma-inducible CIITA expression and can function as nonprofessional antigen presenting cells in endocytic processing and CD4+ T-cell activation. Glia 36, 391\u2013405 (2001)","journal-title":"Glia"},{"key":"BFnature01158_CR22","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1126\/science.277.5332.1630","volume":"277","author":"JE Darnell Jr.","year":"1997","unstructured":"Darnell, J. E. Jr. STATs and gene regulation. Science 277, 1630\u20131635 (1997)","journal-title":"Science"},{"key":"BFnature01158_CR23","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/89058","volume":"7","author":"G Weitz-Schmidt","year":"2001","unstructured":"Weitz-Schmidt, G. et al. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nature Med. 7, 687\u2013692 (2001)","journal-title":"Nature Med."},{"key":"BFnature01158_CR24","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/343425a0","volume":"343","author":"JL Goldstein","year":"1990","unstructured":"Goldstein, J. L. & Brown, M. S. Regulation of the mevalonate pathway. Nature 343, 425\u2013430 (1990)","journal-title":"Nature"},{"key":"BFnature01158_CR25","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.4049\/jimmunol.126.6.2093","volume":"126","author":"JA Cuthbert","year":"1981","unstructured":"Cuthbert, J. A. & Lipsky, P. E. Sterol metabolism and lymphocyte responsiveness: inhibition of endogenous sterol synthesis prevents mitogen-induced human T cell proliferation. J. Immunol. 126, 2093\u20132099 (1981)","journal-title":"J. Immunol."},{"key":"BFnature01158_CR26","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1038\/ni0901-762","volume":"2","author":"L Steinman","year":"2001","unstructured":"Steinman, L. Multiple sclerosis: a two-stage disease. Nature Immunol. 2, 762\u2013764 (2001)","journal-title":"Nature Immunol."},{"key":"BFnature01158_CR27","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/S0304-3940(99)00414-0","volume":"269","author":"R Stanislaus","year":"1999","unstructured":"Stanislaus, R., Pahan, K., Singh, A. K. & Singh, I. Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin. Neurosci. Lett. 269, 71\u201374 (1999)","journal-title":"Neurosci. Lett."},{"key":"BFnature01158_CR28","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/0165-5728(95)00146-8","volume":"63","author":"WS Walker","year":"1995","unstructured":"Walker, W. S., Gatewood, J., Olivas, E., Askew, D. & Havenith, C. E. Mouse microglial cell lines differing in constitutive and interferon-gamma-inducible antigen-presenting activities for naive and memory CD4+ and CD8+ T cells. J. Neuroimmunol. 63, 163\u2013174 (1995)","journal-title":"J. Neuroimmunol."},{"key":"BFnature01158_CR29","doi-asserted-by":"publisher","first-page":"2705","DOI":"10.1002\/(SICI)1521-4141(199909)29:09<2705::AID-IMMU2705>3.0.CO;2-1","volume":"29","author":"F Aloisi","year":"1999","unstructured":"Aloisi, F. et al. Relative efficiency of microglia, astrocytes, dendritic cells and B cells in naive CD4+ T cell priming and Th1\/Th2 cell restimulation. Eur. J. Immunol. 29, 2705\u20132714 (1999)","journal-title":"Eur. J. Immunol."},{"key":"BFnature01158_CR30","doi-asserted-by":"crossref","first-page":"5959","DOI":"10.4049\/jimmunol.161.11.5959","volume":"161","author":"JM Soos","year":"1998","unstructured":"Soos, J. M. et al. Astrocytes express elements of the class II endocytic pathway and process central nervous system autoantigen for presentation for encephalitogenic T cells. J. Immunol. 161, 5959\u20135966 (1998)","journal-title":"J. Immunol."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature01158.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature01158","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature01158.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T14:10:52Z","timestamp":1684419052000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature01158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,11]]},"references-count":30,"journal-issue":{"issue":"6911","published-print":{"date-parts":[[2002,11]]}},"alternative-id":["BFnature01158"],"URL":"https:\/\/doi.org\/10.1038\/nature01158","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1010614.165758","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1010614.160408","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,11]]}}}