Tetra-arsenic tetra-sulfide ameliorates lupus syndromes by inhibiting IL-17 producing double negative T cells

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Tetra-arsenic tetra-sulfide (As4S4), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects. In our previous study, BXSB lupus-prone mice treated with As4S4 has showed improved monocytosis, decreased serum interleukin (IL)-6 and suppressed skin, liver and renal lesions with well-tolerance. In this study, we explored the effect and mechanism of As4S4 on the MRL/lpr mice. MRL/lpr and wild MRL/MpJ mice were divided into control and As4S4 treatment groups and dosed with As4S4 or placebo for 8 weeks. We found that As4S4 prevented the skin, renal and lung lesions of MRL/lpr mice. As4S4 significantly decreased the double negative T (DN T) cells and reduced the serum levels of IL-17, IL-10, and antinuclear antibodies titer. Further results revealed that the FasL was decreased, and activated caspases elevated in DN T cells in As4S4 treated MRL/lpr mice. Taken together, As4S4 could selectively suppresses DN T cells by inducing apoptosis. It also reduced inflammatory cytokines IL-17, which may be produced by DN T cells. As4S4 may represent a new therapy for SLE.