Baumer Yvonne, Singh Komudi, Baez Andrew S, Gutierrez-Huerta Christian A, Chen Long, Igboko Muna, Turner Briana S, Yeboah Josette A, Reger Robert N, Ortiz-Whittingham Lola R, Bleck Christopher K E, Mitchell Valerie M, Collins Billy S, Pirooznia Mehdi, Dagur Pradeep K, Allan David S J, Muallem-Schwartz Daniella, Childs Richard W, Powell-Wiley Tiffany M
Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Bioinformatics and Computational Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
bioRxiv. 2023 Sep 15:2023.09.12.556825. doi: 10.1101/2023.09.12.556825.
Adverse social determinants of health (aSDoH) are associated with obesity and related comorbidities like diabetes, cardiovascular disease, and cancer. Obesity is also associated with natural killer cell (NK) dysregulation, suggesting a potential mechanistic link. Therefore, we measured NK phenotypes and function in a cohort of African-American (AA) women from resource-limited neighborhoods. Obesity was associated with reduced NK cytotoxicity and a shift towards a regulatory phenotype. , LDL promoted NK dysfunction, implicating hyperlipidemia as a mediator of obesity-related immune dysregulation. Dual specific phosphatase 1 (DUSP1) was induced by LDL and was upregulated in NK cells from subjects with obesity, implicating DUSP1 in obesity-mediated NK dysfunction. , DUSP1 repressed LAMP1/CD107a, depleting NK cells of functional lysosomes to prevent degranulation and cytokine secretion. Together, these data provide novel mechanistic links between aSDoH, obesity, and immune dysregulation that could be leveraged to improve outcomes in marginalized populations.
不良健康社会决定因素（aSDoH）与肥胖及糖尿病、心血管疾病和癌症等相关合并症有关。肥胖还与自然杀伤细胞（NK）功能失调有关，提示存在潜在的机制联系。因此，我们在来自资源有限社区的非裔美国（AA）女性队列中测量了NK表型和功能。肥胖与NK细胞毒性降低以及向调节性表型转变有关。低密度脂蛋白（LDL）促进NK功能障碍，表明高脂血症是肥胖相关免疫失调的介质。双特异性磷酸酶1（DUSP1）由LDL诱导，在肥胖受试者的NK细胞中上调，表明DUSP1参与肥胖介导的NK功能障碍。此外，DUSP1抑制溶酶体相关膜蛋白1/CD107a，使NK细胞功能性溶酶体减少，从而阻止脱颗粒和细胞因子分泌。总之，这些数据提供了aSDoH、肥胖和免疫失调之间新的机制联系，可用于改善边缘化人群的健康结局。
