Loss of the innate immunity negative regulator IRAK-M leads to enhanced host immune defense against tumor growth.
Loss of the innate immunity negative regulator IRAK-M leads to enhanced host immune defense against tumor growth.
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先天免疫负调节因子 IRAK-M 的丧失会增强宿主对肿瘤生长的免疫防御。
DOI：
10.1016/j.molimm.2007.03.018
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发表时间：
2007
影响因子：
3.6
通讯作者：
Li,Liwu
中科院分区：
文献类型：
--
作者：
Xie,Qifa;Gan,Lu;Wang,Jianxia;Wilson,Ingred;Li,Liwu
IRAK-M是先天免疫信号传导过程的负调节剂。虽然先天免疫的减弱可能有助于防止过度炎症，但它也可能导致肿瘤细胞的免疫监视受损，并有助于肿瘤的形成和生长。在这里，我们证明了IRAK-M−/−小鼠在接种可移植肿瘤细胞后对肿瘤生长具有抗性。来自IRAK-M−/−小鼠的免疫细胞负责抗肿瘤作用，因为将IRAK-M−/−小鼠的脾细胞过继转移到野生型小鼠可以转移肿瘤抗性表型。在肿瘤细胞激发后，IRAK-M−/−脾细胞中CD 4+和CD 8 +T细胞群升高，CD 4 + CD 25 + Foxp 3+调节性T细胞群降低。此外，我们观察到IRAK-M缺陷导致T细胞和B细胞的增殖和活化升高。IRAK-M缺陷直接导致NFκB活化增强可能解释T和B细胞活化升高。此外，IRAK-M−/−小鼠的巨噬细胞对乙酰化LDL和凋亡胸腺细胞的吞噬功能增强。总的来说，我们证明IRAK-M直接参与先天性和适应性免疫信号传导过程的调节，并且IRAK-M的缺失增强宿主抗肿瘤免疫应答。
IRAK-M is a negative regulator of innate immunity signaling processes. Although attenuation of innate immunity may help to prevent excessive inflammation, it may also lead to compromised immune surveillance of tumor cells and contribute to tumor formation and growth. Here, we demonstrate that IRAK-M−/−mice are resistant to tumor growth upon inoculation with transplantable tumor cells. Immune cells from IRAK-M−/−mice are responsible for the anti-tumor effect, since adoptive transfer of splenocytes from IRAK-M−/−mice to wild type mice can transfer the tumor-resistant phenotype. Upon tumor cell challenge, there are elevated populations of CD4+and CD8+T cells and a decreased population of CD4+CD25+Foxp3+regulatory T cells in IRAK-M−/−splenocytes. Furthermore, we observe that IRAK-M deficiency leads to elevated proliferation and activation of T cells and B cells. Enhanced NFκB activation directly caused by IRAK-M deficiency may explain elevated activation of T and B cells. In addition, macrophages from IRAK-M−/−mice exhibit enhanced phagocytic function toward acetylated LDL and apoptotic thymocytes. Collectively, we demonstrate that IRAK-M is directly involved in the regulation of both innate and adaptive immune signaling processes, and deletion of IRAK-M enhances host anti-tumor immune response.