Rebecca B Delconte, Mark Owyong, Endi K Santosa, Katja Srpan, Sam Sheppard, Tomi J McGuire, Aamna Abbasi, Carlos Diaz-Salazar, Jerold Chun, Inez Rogatsky, Katharine C Hsu, Stefan Jordan, Miriam Merad, Joseph C Sun
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引用次数: 0
摘要
禁食与改善癌症预后有关。在这里,我们研究了禁食对自然杀伤(NK)细胞抗肿瘤免疫力的影响。周期性禁食以一种依赖 NK 细胞的方式提高了对实体瘤和转移性肿瘤的免疫力。禁食期间,NK细胞从外周组织重新分布到骨髓(BM)。在人体中,禁食也会减少循环中的NK细胞数量。禁食小鼠脾脏中的 NK 细胞在脂肪酸和糖皮质激素浓度升高的作用下发生了新陈代谢,通过增加 CPT1A 酶的表达增强了脂肪酸代谢,而 Cpt1a 基因缺失会损害 NK 细胞在这种情况下的存活和功能。与此同时,在禁食期间,NK细胞重新分布到BM需要转运介质S1PR5和CXCR4。白细胞介素(IL)-12表达的基质骨髓细胞池的增加为这些细胞提供了能量,从而改善了IFN-γ的产生。我们的研究结果确定了饮食限制与优化的先天性免疫反应之间的联系,有望加强免疫疗法策略。
Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity.
Fasting is associated with improved outcomes in cancer. Here, we investigated the impact of fasting on natural killer (NK) cell anti-tumor immunity. Cyclic fasting improved immunity against solid and metastatic tumors in an NK cell-dependent manner. During fasting, NK cells underwent redistribution from peripheral tissues to the bone marrow (BM). In humans, fasting also reduced circulating NK cell numbers. NK cells in the spleen of fasted mice were metabolically rewired by elevated concentrations of fatty acids and glucocorticoids, augmenting fatty acid metabolism via increased expression of the enzyme CPT1A, and Cpt1a deletion impaired NK cell survival and function in this setting. In parallel, redistribution of NK cells to the BM during fasting required the trafficking mediators S1PR5 and CXCR4. These cells were primed by an increased pool of interleukin (IL)-12-expressing BM myeloid cells, which improved IFN-γ production. Our findings identify a link between dietary restriction and optimized innate immune responses, with the potential to enhance immunotherapy strategies.
期刊介绍:
Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.