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‐6 (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 (ANA) 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.

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