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

Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Tetra‐arsenic tetra‐sulfide (As 4 S 4 ), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects. In our previous study, BXSB lupus‐prone mice treated with As 4 S 4 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 As 4 S 4 on the MRL/lpr mice. MRL/lpr and wild MRL/MpJ mice were divided into control and As 4 S 4 treatment groups and dosed with As 4 S 4 or placebo for 8 weeks. We found that As 4 S 4 prevented the skin, renal and lung lesions of MRL/lpr mice. As 4 S 4 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 As 4 S 4 treated MRL/lpr mice. Taken together, As 4 S 4 could selectively suppresses DN T cells by inducing apoptosis. It also reduced inflammatory cytokines IL‐17, which may be produced by DN T cells. As 4 S 4 may represent a new therapy for SLE.