Zhang Yingying, Zhang Mengying, Li Xueqin, Tang Zongsheng, He Ling, Lv Kun
Laboratory Medicine of Yijishan Hospital, Wannan Medical College, Wuhu 241001, People's Republic of China.
Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu 241001 People's Republic of China.
Mol Immunol. 2017 Mar;83:62-71. doi: 10.1016/j.molimm.2017.01.013. Epub 2017 Jan 19.
Galectin-9 is known to play a role in the modulation of innate and adaptive immunity to ameliorate CVB3-induced myocarditis. In the present study, we found that galectin-9 induced the expansion of CD11bLy-6C myeloid-derived suppressor cells (MDSCs) in the heart from CVB3-infected mice. Adoptive transfer of CD11bLy-6C MDSCs significantly alleviated myocarditis accompanied by increased Th2 and Treg frequency and anti-inflammatory cytokines expression in the heart tissue. Moreover, Ly6C MDSCs, but not Ly6G cells, expressed Arg-1 and NOS2, and suppressed CD4 T cell proliferation in vitro in an Arg-1-dependent mechanism; an event that was reversed with treatment of either an Arg-1 inhibitor or addition of excess l-arginine. Furthermore, Ly6C MDSCs co-expressed higher levels of F4/80, Tim-3, and IL-4Rα, and had the plasticity to up-regulate NOS2 or Arg-1 in response to IFN-γ or IL-4 treatment. The present results indicate that galectin-9 expands CD11bLy-6C MDSCs to ameliorate CVB3-induced myocarditis.
已知半乳糖凝集素-9在调节先天性和适应性免疫以改善柯萨奇病毒B3（CVB3）诱导的心肌炎中发挥作用。在本研究中，我们发现半乳糖凝集素-9诱导CVB3感染小鼠心脏中CD11bLy-6C髓系来源的抑制性细胞（MDSCs）扩增。过继转移CD11bLy-6C MDSCs可显著减轻心肌炎，同时心脏组织中Th2和调节性T细胞（Treg）频率增加以及抗炎细胞因子表达增加。此外，Ly6C MDSCs而非Ly6G细胞表达精氨酸酶-1（Arg-1）和一氧化氮合酶2（NOS2），并以Arg-1依赖的机制在体外抑制CD4 T细胞增殖；用Arg-1抑制剂处理或添加过量的L-精氨酸可逆转这一现象。此外，Ly6C MDSCs共表达更高水平的F4/80、T细胞免疫球蛋白黏蛋白3（Tim-3）和白细胞介素4受体α（IL-4Rα），并且具有在干扰素-γ（IFN-γ）或白细胞介素4（IL-4）处理下上调NOS2或Arg-1的可塑性。目前的结果表明，半乳糖凝集素-9通过扩增CD11bLy-6C MDSCs来改善CVB3诱导的心肌炎。
