Interleukin-32 positive immune and resident cells in kidney samples from lupus patients: a pilot study

IntroductionLupus nephritis (LN), caused by immune complexes produced in situ 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...

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Main Authors: Simona Truglia, Francesco Ciccia, Silvia Mancuso, Antonella Capozzi, Aroldo Rizzo, Francesca Romana Spinelli, Fulvia Ceccarelli, Tania Colasanti, Cristina Garufi, Francesca Miranda, Maurizio Sorice, Cristiano Alessandri, Fabrizio Conti
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1475073/full
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author Simona Truglia
Simona Truglia
Francesco Ciccia
Silvia Mancuso
Antonella Capozzi
Aroldo Rizzo
Francesca Romana Spinelli
Fulvia Ceccarelli
Tania Colasanti
Cristina Garufi
Francesca Miranda
Maurizio Sorice
Cristiano Alessandri
Fabrizio Conti
author_facet Simona Truglia
Simona Truglia
Francesco Ciccia
Silvia Mancuso
Antonella Capozzi
Aroldo Rizzo
Francesca Romana Spinelli
Fulvia Ceccarelli
Tania Colasanti
Cristina Garufi
Francesca Miranda
Maurizio Sorice
Cristiano Alessandri
Fabrizio Conti
author_sort Simona Truglia
collection DOAJ
description IntroductionLupus nephritis (LN), caused by immune complexes produced in situ 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.MethodsIn 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-κB and IL-32 by Western blot.ResultsWe 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-κB 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.DiscussionThese 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’ antibodies. This study may indicate a possible role for IL-32 in the pathogenesis of LN.
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spelling doaj-art-4bb6860c175943acbe354eb831813b872025-01-06T06:59:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14750731475073Interleukin-32 positive immune and resident cells in kidney samples from lupus patients: a pilot studySimona Truglia0Simona Truglia1Francesco Ciccia2Silvia Mancuso3Antonella Capozzi4Aroldo Rizzo5Francesca Romana Spinelli6Fulvia Ceccarelli7Tania Colasanti8Cristina Garufi9Francesca Miranda10Maurizio Sorice11Cristiano Alessandri12Fabrizio Conti13Rheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, ItalyRheumatology Unit, Department of Internal Medicine and Medical Specialties, Azienda Ospedaliera Universitaria (AOU) Policlinico Umberto I, Rome, ItalyDepartment of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, ItalyRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, Rome, ItalyPathology Section, Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello, Palermo, ItalyRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, ItalyRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, ItalyRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, ItalyRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, ItalyRheumatology Unit, Azienda Sanitaria Locale (ASL) Roma1, Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, Rome, ItalyRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, ItalyRheumatology Unit, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, ItalyIntroductionLupus nephritis (LN), caused by immune complexes produced in situ 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.MethodsIn 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-κB and IL-32 by Western blot.ResultsWe 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-κB 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.DiscussionThese 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’ antibodies. This study may indicate a possible role for IL-32 in the pathogenesis of LN.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1475073/fulllupus nephritistoll like receptor 3interleukin-32lupus nephritis IgGresident renal cells
spellingShingle Simona Truglia
Simona Truglia
Francesco Ciccia
Silvia Mancuso
Antonella Capozzi
Aroldo Rizzo
Francesca Romana Spinelli
Fulvia Ceccarelli
Tania Colasanti
Cristina Garufi
Francesca Miranda
Maurizio Sorice
Cristiano Alessandri
Fabrizio Conti
Interleukin-32 positive immune and resident cells in kidney samples from lupus patients: a pilot study
Frontiers in Immunology
lupus nephritis
toll like receptor 3
interleukin-32
lupus nephritis IgG
resident renal cells
title Interleukin-32 positive immune and resident cells in kidney samples from lupus patients: a pilot study
title_full Interleukin-32 positive immune and resident cells in kidney samples from lupus patients: a pilot study
title_fullStr Interleukin-32 positive immune and resident cells in kidney samples from lupus patients: a pilot study
title_full_unstemmed Interleukin-32 positive immune and resident cells in kidney samples from lupus patients: a pilot study
title_short Interleukin-32 positive immune and resident cells in kidney samples from lupus patients: a pilot study
title_sort interleukin 32 positive immune and resident cells in kidney samples from lupus patients a pilot study
topic lupus nephritis
toll like receptor 3
interleukin-32
lupus nephritis IgG
resident renal cells
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1475073/full
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