{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:45:01Z","timestamp":1790729101473,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In this study, we have investigated the potential regulatory mechanisms of IL\u201035 to relieve lupus nephritis (LN) through regulating Janus kinase (JAK)\/signal transducers and activators of transcription (STAT) signaling pathway in mesangial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 105 significant differentially expressed proteins (DEPs) between juvenile systemic lupus erythematosus (JSLE) patients with LN and healthy controls, LAIR1, PDGFR\u03b2, VTN, EPHB4, and EPHA4 were downregulated in JSLE\u2010LN. They consist of an interactive network with PTPN11 and FN1, which involved in IL\u201035\u2010related JAK\/STAT signaling pathway. Besides, urinary LAIR1 was significantly correlated with JSLE\u2010LN clinical parameters such as SLEDAI\u20102K, %CD19+ B, and %CD3+ T cells. Through bioinformatics analysis of co\u2010immunoprecipitation with mass spectrometry results, including GO, KEGG, and STRING, five genes interacted with Lair1 were upregulated by IL\u201035, but only Myh10 was downregulated. Therefore, we presumed an interactive network among these DEPs, JAK\/STAT, and IL\u201035. Moreover, the downregulated phosphorylated (p)\u2010STAT3, p\u2010p38 MAPK, and p\u2010ERK, and the upregulated p\u2010JAK2\/p\u2010STAT1\/4 in IL\u201035 overexpressed mesangial cells, and RNA\u2010sequencing results validated the potential regulatory mechanisms of IL\u201035 in alleviating JSLE\u2010LN disease. Moreover, the relieved histopathological features of nephritis including urine protein and leukocyte scores, a decreased %CD90\n                      <jats:sup>+<\/jats:sup>\n                      \u03b1SMA\n                      <jats:sup>+<\/jats:sup>\n                      mesangial cells and pro\u2010inflammatory cytokines, the inactivated JAK\/STAT signals and the significant upregulated Tregs in spleen, thymus and peripheral blood were validated in Tregs and IL\u201035 overexpression plasmid\u2010treated lupus mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study provided a reference proteomic map of urinary biomarkers for JSLE\u2010LN and elucidated evidence that IL\u201035 may regulate the interactive network of LAIR1\u2010PTPN11\u2010JAK\u2010STAT\u2010FN1 to affect JAK\/STAT and MAPK signaling pathways to alleviate inflammation in JSLE\u2010LN. This finding may provide a further prospective mechanism for JSLE\u2010LN clinical treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.309","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T09:06:39Z","timestamp":1612343199000},"source":"Crossref","is-referenced-by-count":37,"title":["A novel potential target of IL\u201035\u2010regulated JAK\/STAT signaling pathway in lupus nephritis"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9853-7380","authenticated-orcid":false,"given":"Zhe","family":"Cai","sequence":"first","affiliation":[{"name":"The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical Center, Guangzhou Meidcal University, Guangzhou, China Institute Pasteur of Shanghai Chinese Academy of Science  Shanghai China"},{"name":"Department of Allergy Immunology and Rheumatology Guangzhou Women and Children's Medical Center, Guangzhou Meidcal University  Guangzhou China"},{"name":"Department of Chemical Pathology Prince of Wales Hospital The Chinese University of Hong Kong  Hong Kong China"},{"name":"Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Allergy Immunology and Rheumatology Guangzhou Women and Children's Medical Center, Guangzhou Meidcal University  Guangzhou China"},{"name":"Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Allergy Immunology and Rheumatology Guangzhou Women and Children's Medical Center, Guangzhou Meidcal University  Guangzhou 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