Obesity modulates NK-cell activity via LDL & DUSP1 signaling for Populations with Adverse Social Determinants.

Autor:	Baumer Y; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Singh K; Bioinformatics and Computational Core Facility, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Saurabh A; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Baez AS; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Gutierrez-Huerta CA; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Chen L; Section of Transplantation Immunotherapy, Cellular and Molecular Therapeuti, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Igboko M; Section of Transplantation Immunotherapy, Cellular and Molecular Therapeuti, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Turner BS; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Yeboah JA; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Reger RN; Section of Transplantation Immunotherapy, Cellular and Molecular Therapeuti, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Ortiz-Whittingham LR; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Joshi S; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Andrews MR; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Aquino Peterson EM; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Bleck CK; Electron Microscopy Core Facility, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Mendelsohn LG; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Mitchell VM; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Collins BS; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Redekar NR; Integrative Data Sciences Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America., Kuhn SA; Integrative Data Sciences Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America., Combs CA; Light Microscopy Core, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Pirooznia M; Bioinformatics and Computational Core Facility, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Dagur PK; Flow Cytometry Core, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Allan DS; Section of Transplantation Immunotherapy, Cellular and Molecular Therapeuti, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Muallem-Schwartz D; Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, United States of America., Childs RW; Section of Transplantation Immunotherapy, Cellular and Molecular Therapeuti, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America., Powell-Wiley TM; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2024 Dec 24. Date of Electronic Publication: 2024 Dec 24.
DOI:	10.1172/jci.insight.180606
Abstrakt:	African American (AA) women are disproportionally affected by obesity and hyperlipidemia, particularly in the setting of adverse social determinants of health (aSDoH) contributing to health disparities. Obesity, hyperlipidemia, and aSDoH appear to impair Natural Killer cells (NKs). As potential common underlying mechanisms are largely unknown, we sought to investigate common signaling pathways involved in NK dysfunction related to obesity and hyperlipidemia in AA women from under-resourced neighborhoods. We determined in freshly isolated NKs that obesity and measures of aSDoH are associated with a shift in NK subsets away from CD56dim/CD16+ cytotoxic NKs. Using ex vivo data, we identified LDL as a marker related to NK cell function in an AA population from under-resourced neighborhoods. Additionally, NK cells from AA women with obesity and LDL-treated NK cells displayed a loss in NK cell function. Comparative unbiased RNA sequencing analysis revealed DUSP1 as a common factor. Subsequently, chemical inhibition of DUSP1 and DUSP1 overexpression in NK cells highlighted its significance in NK cell function and lysosome biogenesis in a mTOR/TFEB-related fashion. Our data demonstrate a pathway by which obesity and hyperlipidemia in the setting of aSDoH may relate to NK dysfunction, making DUSP1 an important target for further investigation of health disparities.
Databáze:	MEDLINE
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