Abstract
Mast cell (MC) degranulation is the foundation of the acute phase of allergic rhinitis (AR). Previously, downregulation of GATA binding protein 3 (GATA-3) was shown to suppress MC activation in an AR mouse model. Binding of microRNA-135a (miR-135a) to GATA-3 was also observed, and overexpression of this miRNA decreased GATA-3 mRNA and protein expression. However, the effects of miR-135a on MCs during AR are currently unknown. In the present study, we utilized a lentiviral (LV) vector to intranasally administer miR-135a to ovalbumin (OVA)-sensitized AR mice. Following miR-135a treatment, the total serum IgE concentration observed during AR was significantly reduced. In the nasal mucosa, the expression of T-box expressed in T cells (T-bet) was higher, whereas that of GATA-3 was lower in the AR mice following miRNA treatment. Notably, during AR, the ratio of type 1 T-helper cells (Th1) to type 2 (Th2) cells in the spleen is unbalanced, favoring Th2. However, administering miR-135a to the AR mice appeared to balance this ratio by increasing and decreasing the percentage of Th1 and Th2 cells, respectively. MiR-135a also appeared to strongly suppress the infiltration of eosinophils and MCs into the nasal mucosa, and it was specifically localized in the MCs, suggesting that its influence is modulated through regulation of GATA-3 in these cells. Additional work identifying the full therapeutic potential of miR-135a in the treatment of AR and diseases involving allergen-induced inflammation is warranted.
Highlights
Allergen-induced inflammation of the upper airway, known as allergic rhinitis (AR), is characterized by a variety of symptoms, all of which are caused by an inappropriate or exaggerated immune reaction involving numerous cytokines and pro-inflammatory factors
MiR-135a appeared to strongly suppress the infiltration of eosinophils and Mast cell (MC) into the nasal mucosa, and it was localized in the MCs, suggesting that its influence is modulated through regulation of GATA binding protein 3 (GATA-3) in these cells
We found that miR-135a base pairs to the 30-UTR of GATA3 mRNA and is downregulated during AR in our mouse model 12
Summary
Allergen-induced inflammation of the upper airway, known as allergic rhinitis (AR), is characterized by a variety of symptoms, all of which are caused by an inappropriate or exaggerated immune reaction involving numerous cytokines and pro-inflammatory factors. Mast cells (MCs), the granules in their cytoplasm that are known to contain a variety of powerful biologically active inflammatory mediators, have been shown to play a critical role in AR. MiR-135a Suppresses Allergic Inflammation via GATA-3 in MCs essential for the differentiation of these cells, GATA-3 expression and function are not limited to Th2 cells. GATA-3 transcripts are relatively abundantly expressed in eosinophils and mast cells [3]. GATA family members, GATA-3, may be critical for “hard-wiring” of a common program of gene expression in mast cells and T helper type 2 cells [4]
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