S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4-ERK1/2 Signaling.
S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4-ERK1/2 Signaling.
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S100A4 通过 TLR4-ERK1/2 信号传导保护骨髓源性抑制细胞免遭内源性凋亡
DOI：
10.3389/fimmu.2018.00388
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发表时间：
2018
影响因子：
7.3
通讯作者：
Qin Z
中科院分区：
文献类型：
--
作者：
Li Q;Dai C;Xue R;Wang P;Chen L;Han Y;Erben U;Qin Z
髓系来源的抑制细胞(MDSCs)通常在癌症或慢性炎症期间扩张，并抑制免疫反应。然而，它们在炎症环境中逃脱内在细胞凋亡的潜在机制仍然很大程度上是未知的。在这项研究中，我们在MDSC积聚的小鼠肿瘤模型中研究了这一点。移植到小钙结合蛋白S100A4(S100A4−/−)缺陷小鼠体内的肿瘤自发排斥反应伴随着外周MDSCs的数量减少。这与肿瘤细胞表面S100A4的表达无关。相反，来自S100A4−/−荷瘤小鼠的MDSCs对诱导内源性细胞凋亡的抵抗力减弱。进一步的研究表明，S100A4通过Toll样受体-4/细胞外信号调节的依赖于caspase-9的抑制来保护MDSCs免于凋亡。S100A4对MDSC在炎症环境中的存活至关重要，这一发现可能对癌症或炎症相关疾病的临床治疗具有重要意义。
Myeloid-derived suppressor cells (MDSCs) often expand during cancer or chronic inflammation and dampen immune responses. However, mechanisms underlying their capacity to escape intrinsic apoptosis in the inflammatory environment are still largely unknown. In this study, we investigated this in mouse tumor models with MDSC accumulation. Spontaneous rejection of tumors implanted into mice deficient for the small Ca2+-binding protein S100A4 (S100A4−/−) was accompanied by low numbers of peripheral MDSCs. This was independent of S100A4 expression on tumor cells. In contrast, MDSCs from S100A4−/− tumor-bearing mice showed a diminished resistance to the induction of intrinsic apoptosis. Further studies demonstrated that S100A4 protects MDSCs from apoptosis through toll-like receptor-4/extracellular signal-regulated kinase-dependent caspase-9 inhibition. The finding that S100A4 is critical for MDSC survival in inflammatory environments might have important implications for the clinical treatment of cancer or inflammation-related diseases.