Immunomodulatory effect of IL-35 gene-transfected mesenchymal stem cells on allergic asthma

Asthma is a common respiratory disease that has no definitive treatment at now. Immune response shifting from T helper (Th)1 to the Th2 is a main problem in asthma, and immunomodulation can help to control asthma. IL-35 and mesenchymal stem cells (MSCs) have regulatory effect on the immune system and may have the ability to control asthma pathology. After culturing MSCs, expression vector of IL-35 (pUNO1-mIL35elasti) was transduced to the MSCs, and then, asthmatic mice were treated with MSCs, MSCs-vector, MSCs-vector-IL-35, and no treatment. Airway hyperresponsiveness (AHR), levels of the cytokines, total and ovalbumin (OVA) specific immunoglobulin (Ig)E, LTB4, and LTC4 were measured. Lung tissue histopathology was also done. MSCs were successfully transduced by pUNO1-mIL35elasti vector, and IL-35 was produced in transduced cells. AHR, levels of the cytokines, IgEs, LTs, goblet cell hyperplasia, mucus secretion, peribronchial, and perivascular inflammation were controlled by MSCs therapy. In MSCs-IL-35 group, these controls were stronger than MSCs without IL-35 group. MSCs had strong effect on control of asthma. Transfected MSCs by expressing IL-35 gene could significantly better control allergic asthma symptoms than MSCs without IL-35. In the future, identification of the IL-35 mechanism of action would be useful to improve cytokine-cell based therapies.