{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:23:07Z","timestamp":1779297787650,"version":"3.51.4"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Lupus nephritis (LN), caused by immune complexes produced <jats:italic>in situ<\/jats:italic> or deposited from the bloodstream, is one of the most severe features of Systemic Lupus Erythematosus (SLE) leading to an increased morbidity and mortality. Toll like receptors (TLRs), such as TLR3, TLR7 and TLR9, may play a key role in its pathogenesis. Interleukin-32 (IL-32), a cytokine involved in both innate and adaptive immune responses, has been widely considered in autoimmune-inflammatory rheumatic diseases. This study aims to evaluate the IL-32 role in LN, also investigating the effect of LN patients IgG (LN-IgG) on IL-32 production via TLR3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In LN patients, IL-32 was detected in sera samples by ELISA KIT and in kidney tissue by immunohistochemistry. HEK293\/T3 cells were incubated with LN-IgG and analyzed for TBK1, phospho-p65 NF-\u03baB and IL-32 by Western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrated IL-32 presence in LN patients compared to SLE patients without renal involvement, observing a direct correlation between IL-32 serum levels and disease duration (p=0.02; r 0.2978). Moreover, IL-32 was strongly expressed in renal samples of LN patients. Phosphorylation of TBK1 resulting in NF-\u03baB activation and IL-32 increase was observed in HEK293\/T3 cells following LN-IgG treatment, TLR3 inhibitor using induced a significant reduction in the expression of these molecules.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results showed that IL-32 is up-regulated in the kidney of LN patients suggesting that in renal tissue IL-32 expression could be induced through TLR3 activation by the LN patients\u2019 antibodies. This study may indicate a possible role for IL-32 in the pathogenesis of LN.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1475073","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T07:00:47Z","timestamp":1736146847000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Interleukin-32 positive immune and resident cells in kidney samples from lupus patients: a pilot study"],"prefix":"10.3389","volume":"15","author":[{"given":"Simona","family":"Truglia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Ciccia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Mancuso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Capozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aroldo","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca Romana","family":"Spinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fulvia","family":"Ceccarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Colasanti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Garufi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Sorice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiano","family":"Alessandri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Conti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker101","article-title":"Assessment of a lupus nephritis cohort over a 30-year period","volume":"50","author":"Croca","year":"2011","journal-title":"Rheumatology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000089","article-title":"The pathogenesis, diagnosis and treatment of lupus nephritis","volume":"26","author":"Schwartz","year":"2014","journal-title":"Curr Opin Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/art.42375","article-title":"Incidence, prevalence, and mortality of lupus nephritis: A population-based study over four decades using the lupus midwest network","volume":"75","author":"Hocao\u011f;lu","year":"2023","journal-title":"Arthritis Rheumatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000887","article-title":"Pathogenesis of lupus nephritis: the contribution of immune and kidney resident cells","volume":"35","author":"Bhargava","year":"2023","journal-title":"Curr Opin Rheumatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/139365","article-title":"Autoantibodies and resident renal cells in the pathogenesis of lupus nephritis: getting to know the unknown","volume":"2012","author":"Yung","year":"2012","journal-title":"Clin Dev Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00461","article-title":"Toll-like receptor signaling pathways","volume":"5","author":"Kawasaki","year":"2014","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.812774","article-title":"Toll-like receptor signaling and its role in cell-mediated immunity","volume":"13","author":"Duan","year":"2022","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004100820","article-title":"Viral double-stranded RNA aggravates lupus nephritis through toll-like receptor 3 on glomerular mesangial cells and antigen-presenting cells","volume":"16","author":"Patole","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005070714","article-title":"Toll-like receptor-7 modulates immune complex glomerulonephritis","volume":"17","author":"Pawar","year":"2006","journal-title":"J Am Soc Nephrol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42081","article-title":"TLR8 deficiency leads to autoimmunity in mice","volume":"120","author":"Demaria","year":"2010","journal-title":"J Clin Invest"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13022","article-title":"Relevant genetic polymorphisms and kidney expression of Toll-like receptor (TLR)-5 and TLR-9 in lupus nephritis","volume":"190","author":"Elloumi","year":"2017","journal-title":"Clin Exp Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7697592","article-title":"Kidney expression of toll like receptors in lupus nephritis: quantification and clinicopathological correlations","volume":"2016","author":"Conti","year":"2016","journal-title":"Mediators Inflamm"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12495","article-title":"TLR3\/TRIF signalling pathway regulates IL-32 and IFN-\u03b2 secretion through activation of RIP-1 and TRAF in the human cornea","volume":"19","author":"Park","year":"2015","journal-title":"J Cell Mol Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"R135","DOI":"10.1186\/ar3073","article-title":"Innate immunity triggers IL-32 expression by fibroblast-like synoviocytes in rheumatoid arthritis","volume":"12","author":"Alsaleh","year":"2010","journal-title":"Arthritis Res Ther"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.12.003","article-title":"Interleukin-32: a cytokine and inducer of TNFalpha","volume":"22","author":"Kim","year":"2005","journal-title":"Immunity"},{"key":"B16","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s40001-015-0083-y","article-title":"A panoramic spectrum of complex interplay between the immune system and IL-32 during pathogenesis of various systemic infections and inflammation","volume":"20","author":"Khawar","year":"2015","journal-title":"Eur J Med Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1140373","article-title":"Interleukin-32 as a biomarker in rheumatic diseases: A narrative review","volume":"14","author":"Kwon","year":"2023","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.4110\/in.2014.14.3.123","article-title":"Interleukin-32 in inflammatory autoimmune diseases","volume":"14","author":"Kim","year":"2014","journal-title":"Immune Netw"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1177\/0961203314538108","article-title":"Three cases of lupus nephritis patients with serum interleukin-32g detection","volume":"23","author":"Inoue","year":"2014","journal-title":"Lupus"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13550","article-title":"Interleukin-32\u03b3: Possible association with the activity and development of nephritis in patients with systemic lupus erythematosus","volume":"22","author":"Kwon","year":"2019","journal-title":"Int J Rheum Dis"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214819","article-title":"European League against Rheumatism\/American College of Rheumatology classification criteria for systemic lupus erythematosus","volume":"78","author":"Aringer","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21664","article-title":"American College of Rheumatology. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis","volume":"64","author":"Hahn","year":"2012","journal-title":"Arthritis Care Res (Hoboken"},{"key":"B23","article-title":"Systemic lupus erythematosus disease activity index 2000","volume":"29","author":"Gladman","year":"2002","journal-title":"J Rheumatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.11.023","article-title":"Revision of the International Society of Nephrology\/Renal Pathology Society classification for lupus nephritis: clarification of definitions and modified National Institutes of Health activity and chronicity indices","volume":"93","author":"Bajema","year":"2018","journal-title":"Kidney Int"},{"key":"B25","doi-asserted-by":"publisher","first-page":"FSO242","DOI":"10.4155\/fsoa-2017-0076","article-title":"The urinary and serum levels of IL-32 in children with febrile urinary tract infections","volume":"3","author":"Rafiei","year":"2017","journal-title":"Future Sci OA"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231912044","article-title":"Usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis\/bladder pain syndrome","volume":"23","author":"Jiang","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S275570","article-title":"Serum and urine interleukin-6 and interleukin-8 levels do not differentiate acute pyelonephritis from lower urinary tract infections in children","volume":"13","author":"Al Rushood","year":"2020","journal-title":"J Inflammation Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1129201","article-title":"Antiphospholipid antibodies in patients with stroke during COVID-19: A role in the signaling pathway leading to platelet activation","volume":"14","author":"Capozzi","year":"2023","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004110917","article-title":"Effect of human anti-DNA antibodies on proximal renal tubular epithelial cell cytokine expression: implications on tubulointerstitial inflammation in lupus nephritis","volume":"16","author":"Yung","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2014.01.013","article-title":"Interaction network mapping among IL-32 isoforms","volume":"101","author":"Kang","year":"2014","journal-title":"Biochimie"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00393-013-1274-y","article-title":"Serum levels of cytokines in systemic lupus erythematosus: Association study in a Chinese population","volume":"73","author":"Zhang","year":"2014","journal-title":"Z Rheumatol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2460206","article-title":"Association of plasma IL-32 levels and gene polymorphisms with systemic lupus erythematosus in Chinese han population","volume":"2016","author":"Wang","year":"2016","journal-title":"Dis Markers"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh339","article-title":"Involvement of IL-32 in activation-induced cell death in T cells","volume":"18","author":"Goda","year":"2006","journal-title":"Int Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003996","article-title":"IL-32\u03b3 Induces the maturation of dendritic cells with th1- and th17-polarizing ability through enhanced IL-12 and IL-6 production","volume":"186","author":"Jung","year":"2011","journal-title":"J Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B2000808","article-title":"Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses","volume":"22","author":"Chen","year":"2021","journal-title":"J Zhejiang Univ Sci B"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1475073\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T07:00:50Z","timestamp":1736146850000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1475073\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,6]]},"references-count":35,"alternative-id":["10.3389\/fimmu.2024.1475073"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1475073","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,6]]},"article-number":"1475073"}}