Vitamin D and Exercise Are Major Determinants of Natural Killer Cell Activity, Which Is Age- and Gender-Specific

Abstract

BackgroundThe coronavirus-19 disease (COVID-19) pandemic reminds us of the importance of immune function, even in immunologically normal individuals. Multiple lifestyle factors are known to influence the immune function.ObjectiveThe aim was to investigate the association between NK cell activity (NKA) and multiple factors including vitamin D, physical exercise, age, and gender.MethodsThis was a cross-sectional association study using health check-up and NKA data of 2,095 subjects collected from 2016 to 2018 in a health check-up center in the Republic of Korea. NKA was measured using the interferon-γ (IFN-γ) stimulation method. The association of NKA with 25-(OH)-vitamin D (25(OH)D) and other factors was investigated by multiple logistic regression analysis.ResultsThe average age of subjects was 48.8 ± 11.6 years (52.9% of subjects were female). Among 2,095 subjects, 1,427 had normal NKA (NKA ≥ 500 pg IFN-γ/mL), while 506 had low NKA (100 ≤ NKA < 500 pg/mL), and 162 subjects had very low NKA (NKA < 100 pg/mL). Compared to men with low 25(OH)D serum level (< 20 ng/mL), vitamin D replete men (30–39.9 ng/mL) had significantly lower risk of very low NKA (OR: 0.358; 95% CI: 0.138, 0.929; P = 0.035). In women, both low exercise (OR: 0.529; 95% CI: 0.299, 0.939; P = 0.030) and medium to high exercise (OR: 0.522; 95% CI: 0.277, 0.981; P = 0.043) decreased the risk compared to lack of physical exercise. Interestingly, in men and women older than 60 years, physical exercise significantly decreased the risk. Older-age was associated with increased risk of very low NKA in men, but not in women.ConclusionPhysical exercise and vitamin D were associated with NKA in a gender- and age-dependent manner. Age was a major risk factor of very low NKA in men but not in women.

The association between micronutrients and the SARS-CoV-2-specific antibodies in convalescent patients

“…Micronutrient supplementation in early gestation has gender-differential effects on the immune system in offspring, particularly on an epigenetic level [ 55 ]. Vitamin D modulates the activity of natural killer cells in a gender-dependent manner [ 56 ], presumably via the molecular interaction between estrogen and vitamin D [ 57 ].…”

Cross-Sectional and Time-Dependent Analyses on Inflammatory Markers following Natural Killer Cell Activity

“…This novel assay uses the serum of ex vivo-stimulated whole blood to detect secreted IFN-γ from NK cells as an indicator of NKA [ 8 ]. Using this method, clinical studies have indicated that NKA is a useful marker for different cancers and is related to immunologic conditions such as aging and vitamin D insufficiency [ 9 , 10 , 11 , 12 ].…”

Therapeutic Potential of Innate Lymphoid Cells for Multiple Myeloma Therapy

“…Beyond broad actions to ameliorate ILCs’ function [ 147 , 148 ], interest has emerged on ILC metabolism as a therapeutic target [ 149 , 150 ]. While these enhancements are not specifically directed towards the treatment of MM, CD38 knockout via CRISPR/Cas9 resulted in higher mitochondrial respiratory activity, with improved persistence in ex vivo expanded peripheral blood NK cells directed against MM cells [ 134 ].…”