{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T01:43:27Z","timestamp":1776131007863,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"JSPS\/MEXT KAKENHI","award":["JP 21H04800"],"award-info":[{"award-number":["JP 21H04800"]}]},{"name":"JSPS\/MEXT KAKENHI","award":["JP 22H05184, JP 22K19424, JP 22H05182 and 24K22045"],"award-info":[{"award-number":["JP 22H05184, JP 22K19424, JP 22H05182 and 24K22045"]}]},{"name":"JSPS\/MEXT KAKENHI","award":["JP 23K06504"],"award-info":[{"award-number":["JP 23K06504"]}]},{"name":"The Institute of Medical Science"},{"DOI":"10.13039\/501100004721","name":"The University of Tokyo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004721","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Systemic lupus erythematosus is a systemic autoimmune disease characterized by the production of autoantibodies and damage to multiple organs. Glomerulonephritis, a manifestation involving glomerular deposition of immune complexes and complement components, significantly contributes to disease morbidity. Although an endosomal single-stranded RNA sensor [Toll-like receptor 7 (TLR7)] is known to drive glomerulonephritis by promoting autoantibody production in B cells, the contribution of macrophage TLR7 responses to glomerulonephritis remains poorly understood. Here, we have examined Tlr7\u2012\/\u2012 NZBWF1 (New Zealand Black\/New Zealand White F1) mice and found that TLR7 deficiency ameliorates lupus nephritis by abolishing autoantibody production against RNA-associated antigens, C3 deposition, and macrophage accumulation in glomeruli. Furthermore, TLR7 signaling increased CD31 expression on glomerular endothelial cells and Ly6Clow macrophages but not on T and B cells, suggesting that CD31 mediates TLR7-dependent migration of monocytes into glomeruli. Compared to their splenic counterparts, glomerular macrophages produced IL-1\u03b2 in a TLR7-dependent manner. In addition, single-cell RNA sequencing of glomerular macrophages revealed that TLR7 signaling induced expression of lupus-associated genes, including those encoding Chitinase 3 like 1, ferritin heavy chain 1, IKK\u03b5, and complement factor B (CfB). Although serum CfB did not increase in NZBWF1 mice, TLR7-dependent CfB protein expression was detected in glomerular macrophages. In addition, TLR7 signaling promoted C3 cleavage and deposition predominantly on mesangial cells. These findings suggest that TLR7 responses in glomerular macrophages accelerate the progression of glomerulonephritis in NZBWF1 mice.<\/jats:p>","DOI":"10.1093\/intimm\/dxaf005","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T12:11:09Z","timestamp":1737979869000},"page":"339-353","source":"Crossref","is-referenced-by-count":4,"title":["TLR7 responses in glomerular macrophages accelerate the progression of glomerulonephritis in NZBWF1 mice"],"prefix":"10.1093","volume":"37","author":[{"given":"Reika","family":"Tanaka","sequence":"first","affiliation":[{"name":"Division of Innate Immunity, The Institute of Medical Science, The University of Tokyo , Tokyo 108-8639,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Murakami","sequence":"additional","affiliation":[{"name":"Division of Innate Immunity, The Institute of Medical Science, The University of Tokyo , Tokyo 108-8639,","place":["Japan"]},{"name":"Faculty of Pharmacy, Department of Pharmaceutical Sciences & Research Institute of Pharmaceutical Sciences, Musashino University , Tokyo 202-8585,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothy","family":"Ellis","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences , Yokohama 230-0045,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Seita","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences , Yokohama 230-0045,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wu","family":"Yinga","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Science, Department of Veterinary Medical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo 113-8657,","place":["Japan"]},{"name":"Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo 113-8657,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Kakuta","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Science, Department of Veterinary Medical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo 113-8657,","place":["Japan"]},{"name":"Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo 113-8657,","place":["Japan"]},{"name":"Collaborative Research Institute for Innovative Microbiology, The University of Tokyo , Tokyo 113-8657,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiki","family":"Kumano","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of 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