Participation of CD161⁺ and invariant natural killer T cells in pediatric asthma exacerbations

Abstract

Asthma has been defined as a disease of chronic airway inflammation in which many cells and cellular products participate with variable degrees of airflow obstruction and hyperresponsiveness that lead to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. Prominent among these cellular elements are two cell types referred to as the invariant natural killer T (iNKT) cells and a subpopulation of T cells expressing the molecule CD161, which are both thought to play a role in the pathogenesis of asthma. Although the presence of iNKT and other CD161(+) cells in murine models has been associated with asthma, relatively few studies have been performed in the adult patient with asthma that have been often conflicting and even fewer studies are available in children. The present study was performed to investigate the peripheral blood frequencies of iNKT and CD161(+) T cells in children with asthma. A total of 35 children, 19 stable asthmatic patients, 6 who had experienced an asthmatic attack within 24 hours and had not received any treatment, and 10 healthy controls, aged 6-12 years, were enrolled in the study. iNKT and CD161(+) T-cell frequencies in blood were measured together with quantitative levels of IL-4 and interferon (IFN) γ using a cytofluorimetric approach. The results show that iNKT cells are increased in pediatric asthmatic patients undergoing exacerbations of asthma. These cells also produced less IFN-γ and more IL-4 than children with stable asthma and in healthy control children. These results suggest that iNKT cells might participate in the development of the asthmatic exacerbations. The increased production of IL-4 in conjunction with the decrease of IFN-γ may be mechanistically responsible, at least partially, for the heightening of the immunologic response leading to the asthmatic attack in children. Knowledge of these interactive mechanisms involving the iNKT cell and our understanding of its role in the exacerbation of asthma hold great promise in the development of better diagnostic predictive markers of disease progression as well as new forms of therapeutic interventions.

Increased Th2-like Invariant Natural Killer T cells in Peripheral Blood From Patients With Asthma

“…IL-4 production from α-GalCer-stimulated blood iNKT cells was increased in asthma patients compared to controls 17. In children with asthma, increased IL-4 secretion from iNKT cells has been observed during acute exacerbations compared to those with stable asthma or normal controls 18. These human studies also suggest that blood iNKT cells in asthmatics may be of the Th2-like subset, which is consistent with our findings.…”

“…Regarding IFN-γ from blood iNKT cells, we did not find any significant differences between asthma patients and controls, which is consistent with the findings by Yan-Ming et al17 Carpio-Pedroza et al reported less IFN-γ production from iNKT cells during acute exacerbations of asthmatics 18. In asthma, IFN-γ production from blood iNKT cells may be normal or reduced 17,18…”

β-Catenin is required for the differentiation of iNKT2 and iNKT17 cells that augment IL-25-dependent lung inflammation

“…Finally, our results obtained from the allergic lung inflammation mouse model may be of some clinical importance. Although the precise role for the different human iNKT subsets in the lung and peripheral blood has yet to be clearly defined, correlative studies suggest that iNKT cells are involved in exacerbations of asthma [ 37 , 38 ]. Furthermore, IL-25 has been reported to be increased in asthmatic humans [ 39 ].…”

Natural killer T Cells: A Powerful Via in the Regulation of Non Communicable Chronic Diseases

“…Recent studies have found evidence of CCR9 expression on iNKT cells in peripheral blood as well as in biopsy samples of patients with asthma. The iNKT cells exhibit expression of CCR9 which is stimulated by CCL25 of dendritic cells (and probably epithelial cells), which conditions phosphorylation of CD226, which results in T αβ CD3+ cells being able to target Th2 type response [63,64]. (Figure 2) We consider this information important since most of the recent studies that lay the foundations concerning the presence of these mechanisms have been performed in mice and few in humans, specifically in the relationship of NKT cells and allergy.…”