{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:30:39Z","timestamp":1787761839555,"version":"build-2784847793"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Systemic lupus erythematosus is an autoimmune disease characterized by increased type I IFNs, autoantibodies, and inflammatory-mediated multiorgan damage. TLR7 activation is an important contributor to systemic lupus erythematosus pathogenesis, but the mechanisms by which type I IFNs participate in TLR7-driven pathologic conditions remain uncertain. In this study, we examined the requirement for type I IFNs in TLR7-stimulated lupus nephritis. Lupus-prone NZM2328, INZM (which lack a functional type I IFN receptor), and NZM2328 IL-1\u03b2\u2212\/\u2212 mice were treated at 10 wk of age on the right ear with R848 (TLR7 agonist) or control (DMSO). Autoantibody production and proteinuria were assessed throughout treatment. Multiorgan inflammation was assessed at the time of decline in health. Renal infiltrates and mRNA expression were also examined after 14 d of treatment. Both NZM2328 and INZM mice exhibited a decline in survival after 3\u20134 wk of R848 but not vehicle treatment. Development of splenomegaly and liver inflammation were dependent on type I IFN. Interestingly, autoantibody production, early renal infiltration of dendritic cells, upregulation of IL-1\u03b2, and lupus nephritis occurred independent of type I IFN signaling. Development of TLR7-driven lupus nephritis was not abolished by the deletion of IL-1\u03b2. Thus, although IFN-\u03b1 is sufficient to induce nephritis acceleration, our data emphasize a critical role for IFN-independent signaling in TLR7-mediated lupus nephritis. Further, despite upregulation of IL-1\u03b2 after TLR7 stimulation, deletion of IL-1\u03b2 is not sufficient to reduce lupus nephritis development in this model.<\/jats:p>","DOI":"10.4049\/jimmunol.1701588","type":"journal-article","created":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T16:25:23Z","timestamp":1528475123000},"page":"393-405","source":"Crossref","is-referenced-by-count":33,"title":["TLR7-Mediated Lupus Nephritis Is Independent of Type I IFN Signaling"],"prefix":"10.1093","volume":"201","author":[{"given":"Sonya J","family":"Wolf","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"},{"name":"Immunology Program, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Theros","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammi J","family":"Reed","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4963-7403","authenticated-orcid":false,"given":"Irina L","family":"Grigorova","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6792-8004","authenticated-orcid":false,"given":"Giovanny","family":"Mart\u00ednez-Col\u00f3n","sequence":"additional","affiliation":[{"name":"Immunology Program, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaim O","family":"Jacob","sequence":"additional","affiliation":[{"name":"University of Southern California Keck School of Medicine , Los Angeles, CA 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B","family":"Hodgin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-8945","authenticated-orcid":false,"given":"J Michelle","family":"Kahlenberg","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,7,15]]},"reference":[{"key":"2025030417570203200_r1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1097\/BOR.0b013e32832efff1","article-title":"Pathogenesis of kidney disease in systemic lupus erythematosus","volume":"21","author":"Bagavant","year":"2009","journal-title":"Curr. 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