IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis

dc.contributor.authorRose, Angelika
dc.contributor.authorvon Spee-Mayer, Caroline
dc.contributor.authorKloke, Lutz
dc.contributor.authorWu, Kaiyin
dc.contributor.authorKühl, Anja
dc.contributor.authorEnghard, Philipp
dc.contributor.authorBurmester, Gerd-Rüdiger
dc.contributor.authorRiemekasten, Gabriela
dc.contributor.authorHumrich, Jens
dc.date.accessioned2020-01-30T10:46:53Z
dc.date.available2020-01-30T10:46:53Z
dc.date.issued2019-10-11
dc.date.updated2019-12-12T18:49:28Z
dc.description.abstractAn acquired deficiency of interleukin-2 (IL-2) and related disturbances in regulatory T cell (Treg) homeostasis play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Low-dose IL-2 therapy was shown to restore Treg homeostasis in patients with active SLE and its clinical efficacy is currently evaluated in clinical trials. Lupus nephritis (LN), a challenging organ manifestation in SLE, is characterized by the infiltration of pathogenic CD4+ T cells into the inflamed kidney. However, the role of the Treg-IL-2 axis in the pathogenesis of LN and the mode of action of IL-2 therapy in the inflamed kidneys are still poorly understood. Using the (NZB × NZW) F1 mouse model of SLE we studied whether intrarenal Treg are affected by a shortage of IL-2 in comparison with lymphatic organs and whether and how intrarenal T cells and renal inflammation can be influenced by IL-2 therapy. We found that intrarenal Treg show phenotypic signs that are reminiscent of IL-2 deprivation in parallel to a progressive hyperactivity of intrarenal conventional CD4+ T cells (Tcon). Short-term IL-2 treatment of mice with active LN induced an expansion the intrarenal Treg population whereas long-term IL-2 treatment reduced the activity and proliferation of intrarenal Tcon, which was accompanied by a clinical and histological amelioration of LN. The association of these immune pathologies with IL-2 deficiency and their reversibility by IL-2 therapy provides important rationales for an IL-2-based immunotherapy of LN.en
dc.description.sponsorshipDFG, SFB 650, Zelluläre Ansätze zur Suppression unerwünschter Immunreaktionen - From Bench to Bedsideen
dc.identifier.eissn2073-4409
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/10678
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-9581
dc.language.isoenen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subject.ddc570 Biowissenschaften; Biologiede
dc.subject.otherSLEen
dc.subject.otherlupus nephritisen
dc.subject.otherregulatory T cellen
dc.subject.otherinterleukin-2en
dc.subject.otherimmunotherapyen
dc.titleIL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritisen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.articlenumber1234en
dcterms.bibliographicCitation.doi10.3390/cells8101234en
dcterms.bibliographicCitation.issue10en
dcterms.bibliographicCitation.journaltitleCellsen
dcterms.bibliographicCitation.originalpublishernameMDPIen
dcterms.bibliographicCitation.originalpublisherplaceBaselen
dcterms.bibliographicCitation.volume8en
tub.accessrights.dnbfreeen
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Medizinische Biotechnologiede
tub.affiliation.facultyFak. 3 Prozesswissenschaftende
tub.affiliation.groupFG Medizinische Biotechnologiede
tub.affiliation.instituteInst. Biotechnologiede
tub.publisher.universityorinstitutionTechnische Universität Berlinen

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