IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis
Angelika Rose,
Caroline von Spee-Mayer,
Lutz Kloke,
Kaiyin Wu,
Anja Kühl,
Philipp Enghard,
Gerd-Rüdiger Burmester,
Gabriela Riemekasten,
Jens Y. Humrich
Affiliations
Angelika Rose
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Charitéplatz 1, 10117 Berlin, Germany
Caroline von Spee-Mayer
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Charitéplatz 1, 10117 Berlin, Germany
Lutz Kloke
Institute of Biotechnology, Department of Medical Biotechnology, Technical University Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
Kaiyin Wu
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Pathology, Charitéplatz 1, 10117 Berlin, Germany
Anja Kühl
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department (Gastroenterology, Infectious Diseases and Rheumatology) / Research Center ImmunoSciences (RCIS), Hindenburgdamm 30, 12200 Berlin, Germany
Philipp Enghard
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nephrology and Intensive Care Medicine, Augustenburger Platz, 13353 Berlin, Germany
Gerd-Rüdiger Burmester
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Charitéplatz 1, 10117 Berlin, Germany
Gabriela Riemekasten
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Charitéplatz 1, 10117 Berlin, Germany
Jens Y. Humrich
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Charitéplatz 1, 10117 Berlin, Germany
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.
