Social Determinants modulate NK cell activity via obesity, LDL, and DUSP1 signaling

Author:

Baumer YvonneORCID,Singh Komudi,Baez Andrew S.ORCID,Gutierrez-Huerta Christian A.ORCID,Chen Long,Igboko Muna,Turner Briana S.ORCID,Yeboah Josette A.,Reger Robert N.,Ortiz-Whittingham Lola R.ORCID,Bleck Christopher K.E.ORCID,Mitchell Valerie M.ORCID,Collins Billy S.,Pirooznia MehdiORCID,Dagur Pradeep K.ORCID,Allan David S.J.,Muallem-Schwartz DaniellaORCID,Childs Richard W.,Powell-Wiley Tiffany M.ORCID

Abstract

SummaryAdverse 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.In vitro, 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.In vitro, 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.

Publisher

Cold Spring Harbor Laboratory

Reference93 articles.

1. Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association

2. The Upstream Determinants of Adult Obesity

3. Prevalence of Obesity Among Adults, by Household Income and Education — United States, 2011–2014

4. Food access and obesity;Obesity Reviews,2007

5. Racial and Ethnic Disparities in Adult Obesity in the United States: CDC’s Tracking to Inform State and Local Action;Prev Chronic Dis,2019

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3