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

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

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.

Afiliação

Baumer Y; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Singh K; Bioinformatics and Computational Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Baez AS; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Gutierrez-Huerta CA; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Chen L; Section of Transplantation Immunotherapy, Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Igboko M; Section of Transplantation Immunotherapy, Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Turner BS; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Yeboah JA; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Reger RN; Section of Transplantation Immunotherapy, Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Ortiz-Whittingham LR; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Bleck CKE; Electron Microscopy Core Facility, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Mitchell VM; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Collins BS; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Pirooznia M; Bioinformatics and Computational Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Dagur PK; Flow Cytometry Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Allan DSJ; Section of Transplantation Immunotherapy, Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Muallem-Schwartz D; Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
Childs RW; Section of Transplantation Immunotherapy, Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Powell-Wiley TM; Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

bioRxiv ; 2023 Sep 15.

Article em En | MEDLINE | ID: mdl-37745366

ABSTRACT

ABSTRACT

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. 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.

Palavras-chave

Cardiovascular disease; Health Disparities; Lipids; Lysosomes; NK cells; Obesity; Social Determinants of Health

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Aspecto: Determinantes_sociais_saude / Equity_inequality Idioma: En Revista: BioRxiv Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA

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