State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, China.
Front Immunol. 2019 Jul 17;10:1661. doi: 10.3389/fimmu.2019.01661. eCollection 2019.
Myeloid-derived suppressor cells (MDSCs), which play an important role in tumor and inflammatory diseases, are divided into two subsets CD11bLy6CLy6G monocytic MDSC (Mo-MDSC) and CD11bLy6CLy6G polymorphonuclear MDSC (PMN-MDSC) with different immunosuppressive function. However, it is poorly understood the mechanism(s) to control differentiation of Mo-MDSCs and PMN-MDSCs. Here, we found that β may promote PMN-MDSC but impede differentiation of Mo-MDSCs and . We demonstrated that β mediated differentiation of MDSCs was through downregulating multiple transcripts such as IL4il. β not only bound to C/EBPβ isoform LIP to inhibit the activation of C/EBPβ but also interacted with WDR5 to interrupt the enrichment of H3K4me3 mark on the promoter region of IL4i1. Data also imply that conserved homo β has a similar function with mouse β. Since MDSC subsets exert different suppressive function, β may be acted as a potential therapeutic target for inflammatory and tumor-associated diseases.
髓系来源的抑制细胞 (MDSCs) 在肿瘤和炎症性疾病中发挥重要作用，可分为具有不同免疫抑制功能的两个亚群：CD11b+Ly6C+Ly6G 单核细胞来源的 MDSC (Mo-MDSC) 和 CD11b+Ly6C+Ly6G 多形核 MDSC (PMN-MDSC)。然而，控制 Mo-MDSC 和 PMN-MDSC 分化的机制尚不清楚。在这里，我们发现β可能促进 PMN-MDSC 分化，但抑制 Mo-MDSC 的分化，和。我们证明了β通过下调多个转录本，如 IL4il，来介导 MDSC 的分化。β不仅与 C/EBPβ 同工型 LIP 结合以抑制 C/EBPβ 的激活，还与 WDR5 相互作用以阻断 H3K4me3 标记在 IL4i1 启动子区域的富集。数据还暗示保守同源β具有与小鼠β相似的功能。由于 MDSC 亚群发挥不同的抑制功能，β 可能成为炎症和肿瘤相关疾病的潜在治疗靶点。
