Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Microbiol Immunol. 2023 May;67(5):264-273. doi: 10.1111/1348-0421.13061. Epub 2023 Mar 28.
Dendritic cells (DCs) take up antigens derived from pathogens such as bacteria and viruses, and from tumor cells and induce the activation of antigen-specific T cells through major histocompatibility complex (MHC)-mediated antigen presentation. Mainstream cigarette smoke extract (CSE) has various effects, and the effects of its major components, nicotine and tar, have been analyzed extensively. Recently, the physiological effects of nicotine- and tar-removed CSE (cCSE) have also been reported. However, the effects of cCSE on DC-mediated immune responses remain unknown. In this study, we found that cCSE enhanced lipopolysaccharide (LPS)-stimulated induction of the expression of MHC-I and MHC-II on the cell surface of mouse bone marrow-derived DCs (BMDCs). In contrast, cCSE suppressed the induction of CD86 induced by stimulation with curdlan and interferon-γ (IFN-γ). In addition, cCSE suppressed the production of IL-12, IL-23, and IL-10 by LPS and curdlan stimulation. In the presence of cCSE, LPS-stimulated BMDCs showed enhanced activation of CD4 and CD8 T cells and increased IL-2 production from T cells by antigen presentation in a mixed-leukocyte reaction assay. In contrast, cCSE did not affect the activation of T cells by curdlan- or IFN-γ-stimulated BMDCs, and curdlan-stimulated BMDCs suppressed IL-17 production from T cells and enhanced IFN-γ production. These results suggest that cCSE has different effects on the activation signals induced by LPS, curdlan, and IFN-γ in BMDCs and modulates the antigen presentation function of BMDCs.
树突状细胞 (DCs) 摄取来自细菌和病毒等病原体以及肿瘤细胞的抗原，并通过主要组织相容性复合体 (MHC) 介导的抗原呈递诱导抗原特异性 T 细胞的激活。主流香烟烟雾提取物 (CSE) 具有多种作用，其主要成分尼古丁和焦油的作用已被广泛分析。最近，还报道了去除尼古丁和焦油的 CSE（cCSE）的生理作用。然而，cCSE 对 DC 介导的免疫反应的影响尚不清楚。在这项研究中，我们发现 cCSE 增强了 LPS 刺激诱导的小鼠骨髓来源的树突状细胞 (BMDCs) 表面 MHC-I 和 MHC-II 的表达。相比之下，cCSE 抑制了由 curdlan 和干扰素-γ (IFN-γ) 刺激诱导的 CD86 的诱导。此外，cCSE 抑制了 LPS 和 curdlan 刺激产生的 IL-12、IL-23 和 IL-10。在 cCSE 的存在下，LPS 刺激的 BMDCs 在混合白细胞反应测定中通过抗原呈递显示出对 CD4 和 CD8 T 细胞的激活增强，以及来自 T 细胞的 IL-2 产生增加。相比之下，cCSE 不影响 curdlan 或 IFN-γ 刺激的 BMDCs 对 T 细胞的激活，并且 curdlan 刺激的 BMDCs 抑制 T 细胞产生 IL-17 并增强 IFN-γ 产生。这些结果表明，cCSE 对 LPS、curdlan 和 IFN-γ 在 BMDCs 中诱导的激活信号具有不同的作用，并调节 BMDCs 的抗原呈递功能。
