最近，酒精中毒症的治疗药物二硫化四氨（DSF）由于其抗癌效果被用作再利用药物。尽管树突状细胞（DCs）在免疫稳态和癌症治疗中起着关键作用，但DSF对DCs的存活和功能的影响尚未研究。因此，我们用DSF和脂多糖（LPS）处理骨髓源性DCs，并进行了各种分析。与骨髓细胞和脾细胞相比，DCs对DSF具有较强耐受性，并且细胞毒性较低。在DSF处理后，DCs的存活率和代谢活性几乎没有下降，无论LPS是否存在。DSF不改变LPS处理的DCs的表面标记物（MHC II、CD86、CD40和CD54）的表达、抗原摄取能力或抗原呈递能力。DSF降低了LPS处理的DCs中白细胞介素（IL）-12/23（p40）的产生，但不影响IL-6或肿瘤坏死因子-α的产生。我们认为粒-巨噬细胞集落刺激因子（GM-CSF）是使DCs对DSF引起的细胞毒性具有耐受性的因子。当不给予GM-CSF或其信号被抑制时，DCs对DSF的耐受性降低。此外，GM-CSF上调了转录因子XBP-1的表达，该因子对DCs的存活至关重要。本研究首次证明DSF不改变DCs的功能，具有较低的细胞毒性，并诱导了差异性细胞因子产生。

Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of dendritic cells (DCs) in immune homeostasis and cancer therapy, the effects of DSF on the survival and function of DCs have not yet been studied. Therefore, we treated bone marrow-derived DCs with DSF and lipopolysaccharide (LPS) and performed various analyses. DCs are resistant to DSF and less cytotoxic than bone marrow cells and spleen cells. The viability and metabolic activity of DCs hardly decreased after treatment with DSF in the absence or presence of LPS. DSF did not alter the expression of surface markers (MHC II, CD86, CD40, and CD54), antigen uptake capability, or the antigen-presenting ability of LPS-treated DCs. DSF decreased the production of interleukin (IL)-12/23 (p40), but not IL-6 or tumor necrosis factor-α, in LPS-treated DCs. We considered the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a factor to make DCs resistant to DSF-induced cytotoxicity. The resistance of DCs to DSF decreased when GM-CSF was not given or its signaling was inhibited. Also, GM-CSF upregulated the expression of a transcription factor XBP-1 which is essential for DCs' survival. This study demonstrated for the first time that DSF did not alter the function of DCs, had low cytotoxicity, and induced differential cytokine production.