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FOXP3+ Regulatory T-Cells in Chronic Kidney Disease: Molecular Pathways and Clinical Implications

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Forkhead Transcription Factors

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 665))

Abstract

CD4+/FOXP3+ regulatory T-cells (Tregs) are essential for the maintenance of self-tolerance and Tregs deficiency results in spontaneous autoimmunity in both mice and humans. The forkhead box P3 (FOXP3) expression is required for both survival of Tregs precursors as well as their function. This suggests that Tregs may use multiple mechanisms to limit autoimmunity and may reflect functional heterogeneity among Tregs subsets that localize to distinct tissue environments. Both cell contact- and cytokine-based immunosuppressive mechanisms would require that Tregs be in close proximity to their targets. The fundamental regulatory activity that can be consistently demonstrated by Tregs in vivo and in vitro has stimulated great interest in developing novel strategies for treatingongoing inflammatory conditions. Patients with end-stage kidney disease (ESKD) are known to display a cellular immune dysfunction. Uremic solutes that accumulate during ESKD may be involved in these processes. In these patients, oxidative stress induced by oxLDL may increase Tregs sensitivity to Fas-mediated apoptosis in part as a consequence of 26S proteasome activation. The 26S proteasome, an ATP-dependent multisubunit protease complex found in the cytoplasm and in the nucleus of all eukaryotic cells,constitutes the central proteolytic machinery of the ubiquitin/proteasome system. Considering the effect of uremia and oxLDL, Tregs from patients with ESKD exhibit early cell-cycle arrest and become apoptotic. These phenomena are the consequence of the oxLDL inhibited proteasome proteolytic activity of p27Kip1 and Bax proteins in Tregs. This may be one mechanistic explanation of the cellular immune dysfunction in patients with ESKD and may have important implications in clinics, since this response could contribute to the micro-inflammation and atherogenesis encountered in this population.

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Author information

Authors and Affiliations

  1. Department of Internal Medicine, CHCVs Ii Hopital de Sion, Grand Champsec 80, 1951, Sion, Switzerland

    Pascal Meier

  2. University of Lausanne, Lausanne, Switzerland

    Pascal Meier

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  1. Pascal Meier
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Correspondence to Pascal Meier .

Editor information

Editors and Affiliations

  1. Division of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

  2. Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

  3. Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

  4. Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

  5. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

  6. Institute of Environmental Health Sciences, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

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© 2009 Landes Bioscience and Springer+Business Media

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Meier, P. (2009). FOXP3+ Regulatory T-Cells in Chronic Kidney Disease: Molecular Pathways and Clinical Implications. In: Maiese, K. (eds) Forkhead Transcription Factors. Advances in Experimental Medicine and Biology, vol 665. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1599-3_12

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