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

  • Pascal MeierEmail author
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Chronic Kidney Disease FOXP3 Expression Forkhead Transcription Factor Uremic Solute Proteasomal Protein Degradation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer+Business Media 2009

Authors and Affiliations

  1. 1.Department of Internal MedicineCHCVs Ii Hopital de SionSionSwitzerland
  2. 2.University of LausanneLausanneSwitzerland

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