Foxp3 -Treg Cells Enhanced by Repeated Low-Dose Gamma-Irradiation Attenuate Ovalbumin-Induced Allergic Asthma in Mice

Abstract

Gamma radiation is used for several therapeutic indications such as cancers and autoimmune diseases. Low-dose whole-body γ irradiation has been shown to activate immune responses in several ways, however, the effect and mechanism of irradiation on allergic asthma remains poorly understood. This study investigated whether or not irradiation exacerbates allergic asthma responses and its potential mechanism. C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce asthma. The mice received whole-body irradiation once daily for 3 consecutive days with a dose of 0.667 Gy using (137)Cs γ rays 24 h before every OVA challenge. Repeated low-dose irradiation reduced OVA-specific IgE levels, the number of inflammatory cells including mast cells, goblet cell hyperplasia, collagen deposition, airway hyperresponsiveness, expression of inflammatory cytokines, CCL2/CCR2, as well as nuclear factor kappa B (NF-κB) and activator protein-1 activities. All of these factors were increased in BAL cells and lung tissue of OVA-challenged mice. Irradiation increased the number of Treg cells, expression of interleukin (IL)-10, IL-2 and IL-35 in BAL cells and lung tissue. Irradiation also increased Treg cell-expressed Foxp3 and IL-10 by NF-κB and RUNX1 in OVA-challenged mice. Furthermore, while Treg cell-expressing OX40 and IL-10 were enhanced in lung tissue or act-bone marrow-derived mast cells (BMMCs) with Treg cells, but BMMCs-expressing OX40L and TGF-β were decreased. The data suggest that irradiation enhances Foxp3(+)- and IL-10-producing Treg cells, which reduce OVA-induced allergic airway inflammation and tissue remodeling through the down-regulation of migration by the CCL2/CCR2 axis and activation of mast cells via OX40/OX40L in lung tissue of OVA-challenged mice.

Expression of Airway Remodeling Proteins in Mast Cell Activated by TGF-β Released in OVA-Induced Allergic Responses and Their Inhibition by Low-Dose Irradiation or 8-oxo-dG

“…The dose of radiation exposure was determined in accordance with ''The radioactive half-life table'' provided by the irradiator company (22). org/10.1667/RR13547.1.S1).…”

Effects of Low-Dose-Gamma Rays on the Immune System of Different Animal Models of Disease

“…There were no data concerning Treg cells in the above three reports; however, the Treg population in asthma mice model was recently reported by Park et al (2013a). They showed the Treg cell population was higher in irradiated OVA mice than in OVA or control mice.…”

“…They suggested that Treg cells enhancement/migration by irradiation may exert a suppressive function in airway inflammation and tissue remodeling in allergic N. Shimura and S. Kojima asthma. Their irradiation protocol of Park et al (2013a) (Fig. 7) was completely different from that of Fang et al (2005) (Fig.…”

Chinese herbal medicine formula Gu-Ben-Fang-Xiao-Tang attenuates airway inflammation by modulating Th17/Treg balance in an ovalbumin-induced murine asthma model

“…In human allergy patients, Treg cell numbers decrease in the peripheral blood and BALF, and cannot suppress the cell proliferation and cytokine production of allergen-stimulated CD4 + T cells (24–26). Furthermore, several murine studies have demonstrated that the induction of Treg cell function reverses the airway hyperresponsiveness and protects against experimentally-induced asthma (27,28). In the current study, the results of flow cytometric analysis revealed that OVA challenge was able to significant increase the proportion of Th17 cells and decrease the proportion of Treg cells, resulting in imbalance of the Th17/Treg cell ratio; this suggests that the Th17/Treg imbalance serves an important role in the pathogenesis of asthma.…”