NK cells in childhood obesity are activated, metabolically stressed, and functionally deficient

• DOI: 10.1172/jci.insight.94939
• Publication Date: 2017-12-20T16:01:44Z
• Authors: Laura M. Tobin; Meenal Mavinkurve; Eirin Carolan; David Kinlen; Eoin C. O’Brien; Mark A. Little; David K. Finlay; Declan Cody; Andrew E. Hogan; Donal O’Shea
• Keywords: Cytotoxicity, Immunologic; Male; 0301 basic medicine; Pediatric Obesity; Adolescent; Immunology; 610; NK cells; Lymphocyte Activation; Body Mass Index; 03 medical and health sciences; Inflammation & Infection; Immunology, Inflammation & Infection; Humans; Childhood obesity; Lymphocyte Count; Child; 2. Zero hunger; Immunometabolism; 3. Good health; Killer Cells, Natural; Metabolism; Female; NATURAL KILLER CELL; Insulin Resistance; K562 Cells

Childhood obesity is a major global concern, with over 50 million children now classified as obese. Obesity has been linked to the development of numerous chronic inflammatory diseases, including type 2 diabetes and multiple cancers. NK cells are subset innate effector cells, which play an important role in regulation adipose tissue antitumor immunity. can spontaneously kill transformed coordinate subsequent immune responses through their production cytokines. We investigated effect on cohort obese children, compared healthy weight. demonstrated reduction peripheral cell frequencies childhood inverse correlations body mass index insulin resistance. Compared from normal weight, we show increased activation metabolism (PD-1, mTOR activation, ECAR, mitochondrial ROS), along reduced capacity respond stimulus, ultimately leading loss function (proliferation tumor lysis). Collectively that activated, metabolically stressed, losing ability perform basic duties. Paired obesity, this suggests negative immunity present early life course certainly many years before overt malignancies.