免疫麻痹是严重脓毒症高死亡率的重要原因，但作用机制不详，治疗手段缺乏。IRAK-M是内毒素通路关键负调控因子，我们发现IRAK-M在严重脓毒症患者单核细胞中高表达，在“二次打击”免疫麻痹动物模型上，干扰IRAK-M表达能明显提高动物存活与抗病原微生物感染，由此推测IRAK-M促进脓毒症免疫麻痹，进而深入探索IRAK-M表达调控机制。内毒素处理后的单核细胞IRAK-M表达快速上升，而相对应的是miR320a表达快速下调，且IRAK-M 3’非翻译区序列上含有多个miR320a潜在结合位点，miR320a在严重脓毒症患者单核细胞中低表达，由此推测miR320a能通过负调控IRAK-M表达，抑制脓毒症免疫麻痹。通过验证上述推测，揭示miR320a/IRAK-M在脓毒症免疫麻痹中的调节机制，探索miR320a在对抗脓毒症免疫麻痹中的应用价值，为临床脓毒症诊疗提供更多潜在生物标志物与治疗手段。

Immunoparalysis accounts for high mortality for sepsis, but the underlying mechanism remains largely unknown and the therapeutic approach is lacking. IRAK-M is a key negative regulator for endotoxin signaling. In our previous investigation, we found that IRAK-M was highly expressed in the monocytes isolated from patients with severe sepsis. In “two-hit” animal model of immnuoparalysis, silencing expression of IRAK-M can significantly improve animal survival and alleviate pathogen infection, suggesting IRAK-M promote immunparalysis. We therefore explore the regulatory mechanism for IRAK-M expression. The result demonstrated that endotoxin can trigger a rapid increase in IRAK-M expression, but on the contrary, the miR320a expression was accordingly downregulated. Bioinformatic analysis revealed that there are two potential miR320a binding sites in the 3’-untranslated region of IRAK-M, furthermore, miR320a expression was downregulated in monocytes from patients with severe sepsis. All of these results let us presume that miR320a can suppress sepsis-induced immunoparalysis by negatively regulating IRAK-M expression. To prove the above hypothesis, we initiate this project, and the main purpose of this project is to unveil the regulatory mechanism of miR320a/IRAK-M in sepsis-induced immunoparalysis and to evaluate the possibility of using miR320a in the therapy of immuoparalysis. The results of this project will provide more potential biomarkers and approaches for the diagnosis as well as therapy of sepsis.