C-Kit⁺ progenitors restore rat asthmatic lung function by modulation of T-bet and GATA-3 expression

What is the central question of this study? The aim of the experiment was to highlight the regenerative capacity of bone marrow Kit⁺ cells in the restoration of asthmatic pulmonary function in the rat model. What is the main finding and its importance? Data showed that these cells were recruited successfully to the asthmatic niche after intratracheal administration and accelerated the regeneration of asthmatic lungs by the modulation of inflammation via the control of Gata3 and Tbx21 expression, leading to decreased tracheal responsiveness to methacholine and reduction of pathological remodelling.

Allergic asthma is a T helper (Th) 2 immunological disorder with consequential uncontrolled inflammatory responses. There is an increasing demand to use new methods for the treatment of asthma based on modulation of the Th2-to-Th1 ratio in favour of the Th1 population. Accordingly, we decided to evaluate the effects of intratracheal administration of Kit⁺ bone marrow cells on tracheal responsiveness and the expression of Gata3 and Tbx21 genes. Forty male Wistar rats were allocated  randomly  into four experimental groups: healthy rats (control group), sensitized rats (OVA group), sensitized rats receiving Kit^- cells (OVA+Kit^- group) and sensitized rats receiving Kit⁺ cells (OVA+Kit⁺ group). Total and differential white blood cell counts, tracheal responsiveness to cumulative methacholine concentrations and histopathological analysis were evaluated. The results showed a statistically significant increase in total white blood cell, eosinophil and neutrophil counts, tracheal contractility, Gata3 expression and prototypical histopathology of asthma. Along with these conditions, we found that the number of lymphocytes was decreased and expression of Tbx21 diminished in sensitized rats compared with control animals. Monitoring of labelled tagged cells confirmed successful engraftment of transplanted cells in pulmonary tissue. Juxtaposition of Kit⁺ cells changed the blood leucogram closer to the control values. Kit⁺ cells increased the expression of Tbx21 and suppressed Gata3 (P < 0.05). In the OVA+Kit⁺ group, tracheal responsiveness was improved coincident with increased pulmonary regeneration. In conclusion, this study showed that intratracheal administration of bone marrow-derived Kit⁺ cells, but not Kit^- cells, could be effective in the alleviation of asthma, presumably by the modulation of Gata3 and Tbx21.