Obesity-related Asthma Pathogenesis; Body Mass Index and Natural Killer cells subgroups

Obese asthma (OA) is an important research subject due to its increasing incidence and lack of specific treatment options. Natural Killer (NK) cells' roles are uncertain in OA pathogenesis. In this study, we aimed to explore the impact of NK cells in different subgroups of OA. Adult obese patients have been assessed within one of three groups: obese non-asthmatics, early onset OA (EoOA) and late onset OA (LoOA) group. Percentages of CD3-CD56+ total NK cells, CD3-CD56dim and CD3-CD56bright NK cell subsets, NK cytotoxicity (CD107a expression), NK activity (CD69), intracellular IFN-γ, IL-10, IL-13, IL-17 levels and NK receptors (NKG2D, NKp46i, NKp44) have been investigated in peripheral blood samples by flow cytometry. The effect of IL-12 and IL-23 stimulation has also been analysed. Obese non-asthmatics (n=5), EoOA (n=5) and LoOA (n=8) patients have been included in the study. BMI has been found to be negatively correlated with CD69, NK activity marker, (p=0.022, r=-0.534). NKG2D receptor has been significantly low in CD56dim cells of asthma population (p=0.046). NKp44 receptor expression has significantly increased after IL-12 stimulation in EoOA and control groups (p=0.02). Intracellular IL-10 content has increased in LoOA and control subjects (p=0.018, p=0.03). LoOA patients showed a decreased NK cytotoxicity comparing to the EoOA (p=0.05). Our study suggests an impaired NK receptor expression, activation and reduced cytotoxicity in OA patients together with variances between different subtypes of this phenotype. This data would be beneficial for shedding light to new studies to explain steroid resistance and frequent exacerbations in OA.