IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis
dc.contributor.author | Rose, Angelika | |
dc.contributor.author | von Spee-Mayer, Caroline | |
dc.contributor.author | Kloke, Lutz | |
dc.contributor.author | Wu, Kaiyin | |
dc.contributor.author | Kühl, Anja | |
dc.contributor.author | Enghard, Philipp | |
dc.contributor.author | Burmester, Gerd-Rüdiger | |
dc.contributor.author | Riemekasten, Gabriela | |
dc.contributor.author | Humrich, Jens | |
dc.date.accessioned | 2020-01-30T10:46:53Z | |
dc.date.available | 2020-01-30T10:46:53Z | |
dc.date.issued | 2019-10-11 | |
dc.date.updated | 2019-12-12T18:49:28Z | |
dc.description.abstract | An 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.sponsorship | DFG, SFB 650, Zelluläre Ansätze zur Suppression unerwünschter Immunreaktionen - From Bench to Bedside | en |
dc.identifier.eissn | 2073-4409 | |
dc.identifier.uri | https://depositonce.tu-berlin.de/handle/11303/10678 | |
dc.identifier.uri | http://dx.doi.org/10.14279/depositonce-9581 | |
dc.language.iso | en | en |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en |
dc.subject.ddc | 570 Biowissenschaften; Biologie | de |
dc.subject.other | SLE | en |
dc.subject.other | lupus nephritis | en |
dc.subject.other | regulatory T cell | en |
dc.subject.other | interleukin-2 | en |
dc.subject.other | immunotherapy | en |
dc.title | IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis | en |
dc.type | Article | en |
dc.type.version | publishedVersion | en |
dcterms.bibliographicCitation.articlenumber | 1234 | en |
dcterms.bibliographicCitation.doi | 10.3390/cells8101234 | en |
dcterms.bibliographicCitation.issue | 10 | en |
dcterms.bibliographicCitation.journaltitle | Cells | en |
dcterms.bibliographicCitation.originalpublishername | MDPI | en |
dcterms.bibliographicCitation.originalpublisherplace | Basel | en |
dcterms.bibliographicCitation.volume | 8 | en |
tub.accessrights.dnb | free | en |
tub.affiliation | Fak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Medizinische Biotechnologie | de |
tub.affiliation.faculty | Fak. 3 Prozesswissenschaften | de |
tub.affiliation.group | FG Medizinische Biotechnologie | de |
tub.affiliation.institute | Inst. Biotechnologie | de |
tub.publisher.universityorinstitution | Technische Universität Berlin | en |