INTRODUCTION
Allergic rhinitis (AR) is a non-infectious inflammatory disease of the nasal mucosa which is mainly mediated by IgE and driven by Th2 cells after exposure to allergens. The main clinical symptoms are sneezing, a runny nose, nasal itching, and nasal congestion1. It has been reported that 10–40% of adults worldwide suffer from AR, and in developing countries, the situation is even worse, as the number of cases of AR rapidly increased in recent decades, especially in China2. The main treatment methods for AR are allergen avoidance, drug therapy, and specific immunotherapy3. However, drug therapy can only manage symptoms and cannot reverse or alleviate the immune imbalance. Although specific immunotherapy can desensitize patients to allergens and prevent the development of lesions, it has a long treatment cycle, which tends to result in poor patient compliance and unproductive treatments4. Therefore, it is urgent to find new directions for effective treatment.
Mesenchymal stem cells (MSCs) have the potential for self-renewal and multi-directional differentiation5 and have immunomodulatory functions6. Previous studies have shown that transplantation of MSCs via the tail vein into an AR mouse model can improve symptoms7, 8. Xenogeneic MSCs have also been proven to exert similar therapeutic effects in AR mice9. In addition, MSCs can also reduce the immunological indicators and adjust the Th1/Th2 reaction balance in AR patients10. The application of MSCs has resulted in definite curative effects. However, MSCs have several disadvantages, including vascular obstruction caused by the large cells11, unpredictable differentiation in the host12, and reported concerns regarding the cancer progression13, 14.
It has also been proven that exosomes secreted by MSCs (MSCs-Exo) have the same efficacy as MSCs; more importantly, transplantation with its associated risks can be avoided15. Exosomes are homogenous vesicles with a diameter of 30–150 nm secreted by a variety of cells16. The vesicles contain different types of proteins, nucleotides, and other substances. Cells can swallow the vesicles through endocytosis so that the active substances in the vesicles can function inside the cells17. MSCs-Exo can mimic the functions of MSCs and exert similar immunomodulatory effects18. Moreover, exosomes do not have a nuclear structure and cannot be amplified in the host, and thus they are safer in clinical application19. However, the clinical use of MSCs-Exo to treat AR has never been investigated. In this paper, we show that AR mice treated with MSCs-Exo by intranasal administration showed a significant improvement in behavior and histology via MAPK signaling.