Nötrofilik (Th1-kaynaklı) astım endotipinde doğal öldürücü invariyant T (iNKT) hücrelerinin rolü

Asthma is a common chronic lung disease. It is categorized into two main endotypes called eosinophilic and neutrophilic asthma. The majority of asthma patients suffer from eosinophilic asthma and respond well to current treatments. However, 5-20% of patients with neutrophilic asthma respond poorly. Invariant Natural Killer T (iNKT) cells have been described to enhance airway inflammation in an eosinophilic animal model of asthma. However, their role in neutrophilic asthma has not been clarified so far. We established mouse models to compare neutrophilic and eosinophilic asthma side-by-side. Using 19 parameter-flow cytometry, we analyzed cell frequencies, transcription factor expressions, and cytokine secretions of cell populations recruited to the inflamed lung and its draining lymph nodes. We compared lung inflammation in wild-type and iNKT cell-deficient (Jα18-/-) mice and found that iNKT cells do not affect the disease severity of neutrophilic asthma. Furthermore, we discovered that the composition of macrophage and DC subsets in the airways allows the distinction of the two asthma endotypes. In particular, interstitial macrophages dominated the lungs of eosinophilic airway inflammation, whereas exudate macrophages and plasmacytoid DCs were more abundant in neutrophilic asthma. Moreover, the IL-10 secreting T cells, B cells, iNKT cells, and innate lymphoid cells (ILCs) populations were comparable between the two endotypes. However, we found a unique subpopulation of neutrophils that expresses high levels of MHC class II molecule and could produce IL-10. These neutrophils were abundant in the lung during neutrophilic airway inflammation.