Artikel
IL-2 therapy reduces renal inflammation and cellular activity of intrarenal CD4+ conventional T cells in lupus prone mice with active lupus nephritis
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Autoren
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Angelika Rose
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Caroline von Spee-Mayer
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Anja A. Kühl
- Charité - Universitätsmedizin Berlin, Gastroenterology, Infectiology and Rheumatology and Research Center ImmunoScience (RCIS), Berlin
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Kaiyin Wu
- Charíté- Inuversitätsmedizin Berlin, Nephrologie, Berlin
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Philipp Enghard
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Nephrologie und internistische Intensivmedizin, Berlin
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Lutz Kloke
- TU Berlin, Institut für Biotechnologie, Medizinische Biotechnologie, Berlin
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Jens Humrich
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
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Gabriela Riemekasten
- Klinik für Rheumatologie, Universität zu Lübeck, Lübeck
| Veröffentlicht: | 29. August 2016 |
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Gliederung
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Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an acquired IL-2 deficiency in the peripheral lymphoid organs and peripheral blood of murine and human SLE (Humrich et al. 2010, von Spee-Mayer et al. 2015). Kidney-infiltrating CD4+T cells play a crucial role in the progression of lupus nephritis (LN). However, the role of kidney-infiltrating T cells in the pathogenesis of LN is still not completely understood. The aim of this study was to investigate whether an IL-2 deficiency is also present in the inflamed kidney, thereby contributing to an impaired intrarenal Treg function and renal inflammation. Furthermore it was investigated if an IL-2 therapy can directly act on intrarenal Treg and whether this has consequences on the kidney inflammation.
Methods: Intrarenal CD4+ T cells phenotype of (NZB/W) mice with active LN was assessed and the in vitro IL-2 production of intrarenal CD3+CD4+CD44+ T cells was determined by flow cytometry. Furthermore, NZB/W mice were treated with IL-2 for a total of 31 days. Kidneys were histological scored using the activity index (AI) and the intrarenal CD4+ T cell phenotype was assessed in IL-2 treated mice compared to control mice.
Results: Intrarenal Treg exhibit characteristic signs of IL-2 deprivation in parallel to a progressive hyperactivity of intrarenal Tcon with disease progression. These Treg defects were associated with a diminished production of IL-2 and an increased production of IFNg by kidney-infiltrating Tcon. IL-2 therapy could increase the frequency of intrarenal natural CD25+Helios+Treg, strongly reduced the hyperactivity of intrarenal Tcon, ultimately resulted in a reduced histological AI and prolonged the survival of IL-2 treated mice.
Conclusion: Our data indicate that an IL-2 deficiency is also present in the inflamed kidney, thereby contributing to renal inflammation. On the other hand, long-term IL-2 treatment is able to reduce hyperactivity of intrarenal Tcon and to diminish kidney inflammation in lupus prone mice. This shows the close relation between intrarenal IL-2 deficiency and resultant Treg defects, the Tcon hyperactivity and the severity of LN. These results also provide additional rationales for an IL-2 based immunotherapy to treat patients with SLE, in particular with renal involvement.
