Elevated apoptosis and abnormal apoptosis signaling of regulatory T cells in patients with systemic lupus erythematosus

Abstract

In systemic lupus erythematosus (SLE), immune tolerance is influenced by defects in naturally occurring T cells (Tregs). To investigate the apoptosis rate of Tregs and their suppressive activity in patients with SLE and then to recognize the genes and signaling pathways that cause Treg apoptosis. FACS was used to assess the frequency and apoptosis rates of Tregs in 48 SLE patients and 28 normal controls (NCs). Coculture of Tregs with CD4+CD25−CD127dim/− T cells was used to assess the suppressive activity of Tregs. Microarray analysis was used to generate unstimulated Tregs gene expression profiles from very high activity patients with SLE and NCs. Real-time PCR was used to confirm differential gene expression. In patients with SLE, the frequency of Tregs was substantially reduced compared to Tregs from NCs. Furthermore, Tregs from SLE patients had an elevated rate of apoptosis and a lower suppressing ability than Tregs from NCs. Tregs apoptosis was negatively associated with the total count of Tregs and positively related to disease activity. Unstimulated Tregs gene expression profiles from patients with recent-onset SLE revealed a biological response that can cause apoptosis, partially triggered by stress, DNA damage, and cytokine stimulation. The discovery of pathway-specific expression signatures is a significant step forward in understanding how Tregs defects contribute to the pathogenesis of SLE. Our findings may contribute to the development of new strategies for treating SLE based on abnormal Tregs apoptosis and restoring immune homeostasis in patients with SLE.