Bcl-xL is required for the development of functional regulatory CD4 cells in lupus-afflicted mice following treatment with a tolerogenic peptide

Amir Sharabi, Smadar Lapter, Edna Mozes

Research output: Contribution to journalArticlepeer-review

Abstract

Dysregulated expression of Bcl-xL and Bcl-2 may initiate the development of autoimmune diseases including systemic lupus erythematosus (SLE). A tolerogenic peptide designated hCDR1 was shown to ameliorate manifestations of spontaneous and induced murine SLE. Recently, we demonstrated that Bcl-xL plays a critical role in the modulating effects of hCDR1, as manifested by reducing the state of activation of lymphocytes and by down-regulating the secretion of the pathogenic cytokines, IFN-γ and IL-10. Here we studied the role of Bcl-xL in the development and function of CD4 regulatory T-cells (Treg) from hCDR1-treated, SLE-afflicted (New-Zealand-Black × New-Zealand-White) F1 mice. We report that Bcl-xL was up-regulated in CD4 Treg of tolerized mice, where it played a role in inducing the regulatory/inhibitory molecules Foxp3, CTLA-4, and TGF-β and in repressing PD-1. Further, Bcl-xL mediated the induction of CTLA-4 and TGF-β in effector T cells (Teff) by CD4 Treg of the tolerized mice. The induction of Bcl-xL in Teff by Treg was TGF-β dependent and CTLA-4 independent, leading to inhibition of proliferation and to a decrease in activated Teff. We conclude that Bcl-xL is required for the development and function of CD4 Treg, which ameliorate lupus following treatment with a tolerogenic peptide.

Original languageEnglish
Pages (from-to)87-95
Number of pages9
JournalJournal of Autoimmunity
Volume34
Issue number2
DOIs
StatePublished - Mar 2010
Externally publishedYes

Keywords

  • Bcl-xL
  • Immunosuppressive molecules
  • Regulatory T cells
  • Systemic lupus erythematosus
  • Tolerogenic peptides

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