Immunomodulatory effect of tonsil-derived mesenchymal stem cells in a mouse model of allergic rhinitis.

Abstract

Although several studies have claimed that mesenchymal stem cells (MSC) derived from human tissues can ameliorate allergic airway inflammation, the immunomodulatory mechanism of MSCs remains unclear. We aimed to determine the effects and the underlying mechanism of tonsil-derived MSCs (T-MSC) on allergic inflammation compared with adipose tissue-derived stem cells (ASC) in a mouse model of allergic rhinitis (AR). MSCs were isolated from human palatine tonsil (T-MSC) and the surface markers were analyzed. The effect of T-MSCs was evaluated in 24 BALB/c mice that were randomly divided into four groups (negative control group, positive control group, T-MSC group, and ASC group). MSCs were administered intravenously to ovalbumin (OVA) sensitized mice (T-MSC and ASC groups) on days 18 to 23, and subsequent OVA challenge was conducted daily from days 24 to 28. Several parameters of allergic inflammation were assessed. T-MSC and ASC had similar characteristics in surface markers. Intravenous injection of T-MSC significantly reduced allergic symptoms, eosinophil infiltration, serum total, and OVA-specific immunoglobulin E (IgE), and the nasal and systemic T-helper (Th) 2 cytokine profile. Further analysis revealed that nasal innate cytokines, such as interleukin (IL) 25 and IL-33, and chemokines, such as CCL11, CCL24, induction was suppressed in T-MSCs injected groups, which explained their underlying mechanism. In addition, the T-MSC group had more inhibition of allergic inflammation than did the ASC group, which might be attributed to the more proliferative activity of T-MSC. Administration of T-MSC effectively reduced allergic symptoms and inflammatory parameters in the mouse model of AR. T-MSC treatment reduced Th2 cytokines and OVA-specific IgE secretion from B cells. In addition, innate cytokine (IL-25 and IL-33) expression and eotaxin messenger RNA expression was inhibited in the nasal mucosa, which is suggestive of the mechanism of reduced allergic inflammation. Therefore, T-MSC treatment is potentially an alternative therapeutic modality in AR.