The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510900, China.
Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, China.
Int J Biol Sci. 2022 Jan 26;18(4):1580-1593. doi: 10.7150/ijbs.68865. eCollection 2022.
Mannan-binding lectin (MBL), a soluble pattern recognition molecule in the innate immune system, is reported to be associated with the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are mainly characterized by immunosuppressive activities involving several inflammatory diseases such as cancer, infection, and arthritis. Some of the factors inducing their apoptosis are known, however, mechanisms have not been identified. The underlying impact of MBL on the MDSCs especially under inflammatory conditions remains unknown. This study was designed to investigate whether MBL affects MDSCs survival during inflammation conditions. WT and MBL-deficient (MBL) mice were induced on day 0 of the experiment by subcutaneous injection of complete Freund's adjuvant and then injected with incomplete Freund's adjuvant into the knee joint space under general anesthesia on day 14 to induce inflammatory arthritis. The proportions of MDSCs in the spleen and blood and the serum level of the inflammatory cytokines were measured. In vitro study, MDSCs were isolated from the bone marrow of WT and MBL mice and cultured in the presence of interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for 5 days with or without tumor necrosis factor-alpha (TNF-α). After adjuvant treatment, MBL mice had a significantly lower frequency of MDSCs as well as elevated serum inflammatory cytokines levels compared to WT mice. MBL deficiency markedly inhibited the MDSCs frequency from mice bone marrow induced by IL-6 and GM-CSF in the presence of TNF-α . Mechanistic studies established that MBL inhibited MDSCs apoptosis via down-regulation of TNF-α/tumor necrosis factor-alpha receptor 1 (TNFR1) signaling pathway and subsequent caspase 3-dependent manner. Mannan-binding lectin deficiency inhibits myeloid-derived suppressor cells expansion via modulating TNF-α triggered apoptosis.
甘露聚糖结合凝集素（MBL）是先天免疫系统中一种可溶性模式识别分子，据报道与免疫细胞的功能有关。髓源抑制细胞（MDSCs）主要特征是具有抑制免疫活性，涉及多种炎症性疾病，如癌症、感染和关节炎。已知一些诱导其凋亡的因素，但是，机制尚未确定。MBL 对 MDSCs 的潜在影响，特别是在炎症条件下，仍然未知。本研究旨在探讨 MBL 是否影响 MDSCs 在炎症条件下的存活。在实验的第 0 天，WT 和 MBL 缺陷（MBL）小鼠通过皮下注射完全弗氏佐剂诱导，然后在全麻下第 14 天向膝关节腔内注射不完全弗氏佐剂诱导炎症性关节炎。测量脾脏和血液中 MDSCs 的比例以及血清中炎症细胞因子的水平。在体外研究中，从 WT 和 MBL 小鼠的骨髓中分离 MDSCs，并在白细胞介素 6（IL-6）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）存在下培养 5 天，有或没有肿瘤坏死因子-α（TNF-α）。在佐剂处理后，与 WT 小鼠相比，MBL 小鼠的 MDSCs 频率明显降低，血清炎症细胞因子水平升高。MBL 缺乏显著抑制了来自 MBL 缺陷小鼠骨髓的 MDSCs 频率，这些细胞在 TNF-α存在下由 IL-6 和 GM-CSF 诱导。机制研究表明，MBL 通过下调 TNF-α/肿瘤坏死因子-α受体 1（TNFR1）信号通路和随后的半胱天冬酶 3 依赖性方式抑制 MDSCs 凋亡。甘露聚糖结合凝集素缺乏通过调节 TNF-α 触发的凋亡来抑制髓源抑制细胞的扩增。
