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

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 e...

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Autores principales: Rose, Angelika, von Spee-Mayer, Caroline, Kloke, Lutz, Wu, Kaiyin, Kühl, Anja, Enghard, Philipp, Burmester, Gerd-Rüdiger, Riemekasten, Gabriela, Humrich, Jens Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829607/
https://www.ncbi.nlm.nih.gov/pubmed/31614462
http://dx.doi.org/10.3390/cells8101234
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author Rose, Angelika
von Spee-Mayer, Caroline
Kloke, Lutz
Wu, Kaiyin
Kühl, Anja
Enghard, Philipp
Burmester, Gerd-Rüdiger
Riemekasten, Gabriela
Humrich, Jens Y.
author_facet Rose, Angelika
von Spee-Mayer, Caroline
Kloke, Lutz
Wu, Kaiyin
Kühl, Anja
Enghard, Philipp
Burmester, Gerd-Rüdiger
Riemekasten, Gabriela
Humrich, Jens Y.
author_sort Rose, Angelika
collection PubMed
description 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.
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spelling pubmed-68296072019-11-18 IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis Rose, Angelika von Spee-Mayer, Caroline Kloke, Lutz Wu, Kaiyin Kühl, Anja Enghard, Philipp Burmester, Gerd-Rüdiger Riemekasten, Gabriela Humrich, Jens Y. Cells Article 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. MDPI 2019-10-11 /pmc/articles/PMC6829607/ /pubmed/31614462 http://dx.doi.org/10.3390/cells8101234 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rose, Angelika
von Spee-Mayer, Caroline
Kloke, Lutz
Wu, Kaiyin
Kühl, Anja
Enghard, Philipp
Burmester, Gerd-Rüdiger
Riemekasten, Gabriela
Humrich, Jens Y.
IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis
title IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis
title_full IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis
title_fullStr IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis
title_full_unstemmed IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis
title_short IL-2 Therapy Diminishes Renal Inflammation and the Activity of Kidney-Infiltrating CD4+ T Cells in Murine Lupus Nephritis
title_sort il-2 therapy diminishes renal inflammation and the activity of kidney-infiltrating cd4+ t cells in murine lupus nephritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829607/
https://www.ncbi.nlm.nih.gov/pubmed/31614462
http://dx.doi.org/10.3390/cells8101234
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