A recent study revealed a novel mechanism by which radiotherapy promotes distant metastatic growth by inducing amphiregulin(AREG)secretion from tumor cells.1 Specifically,tumor-derived AREG reprograms mononuclear phag...A recent study revealed a novel mechanism by which radiotherapy promotes distant metastatic growth by inducing amphiregulin(AREG)secretion from tumor cells.1 Specifically,tumor-derived AREG reprograms mononuclear phagocytes(MNPs)into an immunosuppressive phenotype by activating the epidermal growth factor receptor(EGFR)on their surface.Concurrently,AREG upregulates CD47 expression on tumor cells via the signal transducer and activator of transcription 3(STAT3)pathway,which inhibits phagocytic function and facilitates metastatic progression.This discovery challenges the conventional understanding of the systemic effects of radiotherapy.It also identifies combinatorial therapeutic targets that promise an improvement in radiotherapy efficacy and enable the formulation of personalized treatment strategies.展开更多
Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of the immune response in renal inflammatory diseases such as lupus nephritis. However, the mechanisms underlying ILC2 adhesion and migration in the ...Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of the immune response in renal inflammatory diseases such as lupus nephritis. However, the mechanisms underlying ILC2 adhesion and migration in the kidney remain poorly understood. Here, we revealed the critical role of integrin α4β7 in mediating renal ILC2 adhesion and function. We found that integrin α4β7 enables the retention of ILC2s in the kidney by binding to VCAM-1, E-cadherin, or fibronectin on structural cells. Moreover, integrin α4β7 knockdown reduced the production of the reparative cytokine amphiregulin (Areg) by ILC2s. In lupus nephritis, TLR7/9 signaling within the kidney microenvironment downregulates integrin α4β7 expression, leading to decreased Areg production and promoting the egress of ILC2s. Notably, IL-33 treatment upregulated integrin α4β7 and Areg expression in ILC2s, thereby enhancing survival and reducing inflammation in lupus nephritis. Together, these findings highlight the potential of targeting ILC2 adhesion as a therapeutic strategy for autoimmune kidney diseases.展开更多
骨骼肌衰减症以及损伤或萎缩后肌肉再生修复的相关缺陷是人口老龄化结构中的一个主要公共健康问题,对行动能力、独立性和生活质量产生严重影响,并缺乏真正有效的预防与治疗策略。肌肉损伤后启动了一个高度协调的修复过程,存在一个由免...骨骼肌衰减症以及损伤或萎缩后肌肉再生修复的相关缺陷是人口老龄化结构中的一个主要公共健康问题,对行动能力、独立性和生活质量产生严重影响,并缺乏真正有效的预防与治疗策略。肌肉损伤后启动了一个高度协调的修复过程,存在一个由免疫、炎症细胞、细胞因子以及影响肌肉干细胞增殖和分化生长因子组成的复杂网络。调节性T细胞(regulatory T cells,Treg)在肌肉损伤修复与再生过程发挥不可或缺的作用,Treg细胞通过IL-33∶ST2蛋白轴的作用激活,并被大量招募至损伤部位,促进M1促炎症表型巨噬细胞向M2抗炎表型巨噬细胞转换并释放特殊生长因子双调节素Areg,刺激肌卫星细胞分化和肌肉再生。这些研究证据支持Treg细胞作为慢性肌肉疾病、肌肉衰减症等肌肉损伤或萎缩疾病的潜在治疗靶点,并证明了免疫机制在骨骼肌组织修复中具有核心的稳态作用,为慢性肌肉疾病和衰老肌肉的再生医学研究和治疗开辟了新的前景。展开更多
基金supported by the National Natural Science Foundation of China(32000799)the Natural Science Foundation of Zhejiang Province,China(D25H300005)+1 种基金Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project(GZY-KJS-ZJ-2025-072)Wenzhou Basic Scientific Research Project(Y20240675).
文摘A recent study revealed a novel mechanism by which radiotherapy promotes distant metastatic growth by inducing amphiregulin(AREG)secretion from tumor cells.1 Specifically,tumor-derived AREG reprograms mononuclear phagocytes(MNPs)into an immunosuppressive phenotype by activating the epidermal growth factor receptor(EGFR)on their surface.Concurrently,AREG upregulates CD47 expression on tumor cells via the signal transducer and activator of transcription 3(STAT3)pathway,which inhibits phagocytic function and facilitates metastatic progression.This discovery challenges the conventional understanding of the systemic effects of radiotherapy.It also identifies combinatorial therapeutic targets that promise an improvement in radiotherapy efficacy and enable the formulation of personalized treatment strategies.
基金supported by grants from the National Research Foundation of Korea(SRC2017R1A5A1014560,RS-2023-00217798,RS-2023-00211566 and NRF-2022R1A2C3007730)。
文摘Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of the immune response in renal inflammatory diseases such as lupus nephritis. However, the mechanisms underlying ILC2 adhesion and migration in the kidney remain poorly understood. Here, we revealed the critical role of integrin α4β7 in mediating renal ILC2 adhesion and function. We found that integrin α4β7 enables the retention of ILC2s in the kidney by binding to VCAM-1, E-cadherin, or fibronectin on structural cells. Moreover, integrin α4β7 knockdown reduced the production of the reparative cytokine amphiregulin (Areg) by ILC2s. In lupus nephritis, TLR7/9 signaling within the kidney microenvironment downregulates integrin α4β7 expression, leading to decreased Areg production and promoting the egress of ILC2s. Notably, IL-33 treatment upregulated integrin α4β7 and Areg expression in ILC2s, thereby enhancing survival and reducing inflammation in lupus nephritis. Together, these findings highlight the potential of targeting ILC2 adhesion as a therapeutic strategy for autoimmune kidney diseases.
文摘骨骼肌衰减症以及损伤或萎缩后肌肉再生修复的相关缺陷是人口老龄化结构中的一个主要公共健康问题,对行动能力、独立性和生活质量产生严重影响,并缺乏真正有效的预防与治疗策略。肌肉损伤后启动了一个高度协调的修复过程,存在一个由免疫、炎症细胞、细胞因子以及影响肌肉干细胞增殖和分化生长因子组成的复杂网络。调节性T细胞(regulatory T cells,Treg)在肌肉损伤修复与再生过程发挥不可或缺的作用,Treg细胞通过IL-33∶ST2蛋白轴的作用激活,并被大量招募至损伤部位,促进M1促炎症表型巨噬细胞向M2抗炎表型巨噬细胞转换并释放特殊生长因子双调节素Areg,刺激肌卫星细胞分化和肌肉再生。这些研究证据支持Treg细胞作为慢性肌肉疾病、肌肉衰减症等肌肉损伤或萎缩疾病的潜在治疗靶点,并证明了免疫机制在骨骼肌组织修复中具有核心的稳态作用,为慢性肌肉疾病和衰老肌肉的再生医学研究和治疗开辟了新的前景。
