脓毒症是危重病患者最主要的死亡原因，免疫稳态失衡是脓毒症进展的关键环节。II型固有淋巴细胞（ILC2）是具有固有免疫功能的细胞，参与脓毒症的发生发展。我们曾报道肺ILC2抑制脓毒症肺内皮细胞焦亡，而后续研究发现肺脏募集的ILC2来源于骨髓。GRK2是一种G蛋白偶联受体激酶（GRKs），能调控G蛋白偶联受体内化。下调G蛋白偶联受体CXCR4能促进ILC2从骨髓迁出。我们前期研究发现，GRK2表达于骨髓ILC2，且能下调ILC2表面CXCR4，从而推测其在ILC2的骨髓动员中发挥重要作用，但机制不明。本课题拟利用嵌合体、基因敲除小鼠脓毒症模型，阐明脓毒症时ILC2骨髓动员和肺脏迁移的机制。着重揭示GRK2对CXCR4内化与功能的调控机制，及其在ILC2骨髓动员中的作用。并将进一步探讨上游信号对GRK2的调控作用与机制，从而完善脓毒症免疫稳态调控机制，为脓毒症的免疫调控和治疗提供新的理论依据。

Sepsis is the most important reason of death in critical ill patients. Organ dysfunction is the key process of sepsis. Group 2 Innate lymphoid cells (ILC2) is a newly identified member of innate immunity, which plays a significant role in sepsis. We found that lung ILC2 protects lung endothelial cells from pyroptosis in sepsis. Sepsis-induced expanded lung ILC2 migrated from bone marrow. CXCR4, a type of G protein-coupled receptor, mediates the retention of ILC2 in bone marrow. GRK2, a type of G protein-coupled receptor kinase (GRKs), modulates the internalization of G protein-coupled receptor. Our previous studies have found GRK2 expressed in bone marrow ILC2 and down-regulated the expression of CXCR4 on ILC2. Thus, we speculate that GRK2 may actuate the mobilization of bone marrow ILC2, however, the underlying mechanism still remains unknown. Utilizing Chimera and knock-out mice to perform CLP model, we aim to identify the mechanism of bone marrow ILC2 mobilization and migration into lung in sepsis, elaborate the significant mechanism of GRK2 in regulating CXCR4 internalization and the role of GRK2 in bone marrow ILC2 mobilization in sepsis. Moreover, this project will further explore the role and molecular mechanism of upstream signaling in regulating GRK2. As the significant role of ILC2 in sepsis, this work will lay the foundation for the immune regulation and therapy of sepsis.