{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:56:43Z","timestamp":1759971403740,"version":"build-2065373602"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T00:00:00Z","timestamp":1461715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Type I interferon (IFN) signaling is a central pathogenic pathway in systemic lupus erythematosus (SLE), and therapeutics targeting type I IFN signaling are in development. Multiple proteins with overlapping functions play a role in IFN signaling, but the signaling events downstream of receptor engagement are unclear. This study was undertaken to investigate the roles of the type I and type II IFN signaling components IFN\u2010\u03b1\/\u03b2\/\u03c9 receptor 2 (IFNAR\u20102), IFN regulatory factor 9 (IRF\u20109), and STAT\u20101 in a mouse model of SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used immunohistochemical staining and highly multiplexed assays to characterize pathologic changes in histology, autoantibody production, cytokine\/chemokine profiles, and STAT phosphorylation in order to investigate the individual roles of IFNAR\u20102, IRF\u20109, and STAT\u20101 in MRL\/<jats:italic>lpr<\/jats:italic> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that STAT\u20101<jats:sup>\u2212\/\u2212<\/jats:sup> mice, but not IRF\u20109<jats:sup>\u2212\/\u2212<\/jats:sup> or IFNAR\u20102<jats:sup>\u2212\/\u2212<\/jats:sup> mice, developed interstitial nephritis characterized by infiltration with retinoic acid receptor\u2013related orphan nuclear receptor \u03b3t\u2013positive lymphocytes, macrophages, and eosinophils. Despite pronounced interstitial kidney disease and abnormal kidney function, STAT\u20101<jats:sup>\u2212\/\u2212<\/jats:sup> mice had decreased proteinuria, glomerulonephritis, and autoantibody production. Phosphospecific flow cytometry revealed shunting of STAT phosphorylation from STAT\u20101 to STAT\u20103\/4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We describe unique contributions of STAT\u20101 to pathology in different kidney compartments in a mouse model, and provide potentially novel insight into tubulointerstitial nephritis, a poorly understood complication that predicts end\u2010stage kidney disease in SLE patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39535","type":"journal-article","created":{"date-parts":[[2015,12,4]],"date-time":"2015-12-04T19:11:54Z","timestamp":1449256314000},"page":"1233-1244","source":"Crossref","is-referenced-by-count":9,"title":["Development of Th17\u2010Associated Interstitial Kidney Inflammation in Lupus\u2010Prone Mice Lacking the Gene Encoding STAT\u20101"],"prefix":"10.1002","volume":"68","author":[{"given":"Gloria","family":"Yiu","sequence":"first","affiliation":[{"name":"Stanford University School of Medicine Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tue K.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine, Stanford, California, and Aarhus University Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahareh","family":"Ajami","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3687-264X","authenticated-orcid":false,"given":"David J.","family":"Haddon","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvina D.","family":"Chu","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Tangsombatvisit","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winston A.","family":"Haynes","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian","family":"Diep","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry","family":"Steinman","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine and Institute for Immunity, Transplantation, and Infection Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Faix","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Utz","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine and Institute for Immunity, Transplantation, and Infection Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,4,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.157"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37824"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/02841869109092414"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0337679100"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350606"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400928"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030491"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364421"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021996"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-8411(02)00109-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.3.2134"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30065"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2771"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780381016"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60342-9"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.1.305"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00766.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20441"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1984.75"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108626"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.4049\/jimmunol.139.10.3287","article-title":"Polyreactive autoantibodies are nephritogenic in murine lupus nephritis","volume":"139","author":"Pankewycz OG","year":"1987","journal-title":"J Immunol"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30392"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203312457718"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.01.019"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.07.004"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24499"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3523"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3707"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0302-295"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2913"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.7423"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.091062498"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1711.2005.01389.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00291"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.103.029884"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90141-8"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006756"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12035"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1159\/000184012"},{"key":"e_1_2_7_41_1","first-page":"115","article-title":"Long\u2010term prognosis of focal sclerosing glomerulonephritis: an analysis of 250 cases with particular regard to tubulointerstitial changes","volume":"33","author":"Wehrmann M","year":"1990","journal-title":"Clin Nephrol"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni0407-345"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1191\/096120300678828703"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.12.8761"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2009.04031.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364286"},{"key":"e_1_2_7_47_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.4049\/jimmunol.161.1.494","article-title":"IFN\u2010\u03b3 receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL\u2010Faslpr mice","volume":"161","author":"Schwarting A","journal-title":"J Immunol"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1995"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.1999.087"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1209724109"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2667"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201477"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1422.002"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.39535","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.39535","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T13:36:08Z","timestamp":1759930568000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.39535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,27]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1002\/art.39535"],"URL":"https:\/\/doi.org\/10.1002\/art.39535","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"type":"print","value":"2326-5191"},{"type":"electronic","value":"2326-5205"}],"subject":[],"published":{"date-parts":[[2016,4,27]]}}}