Allergic rhinitis (AR) has long been considered to predominantly involve the actions of Th2 cells, with relatively small contributions from Th1 cells. In recent years, the discovery of Th17 and regulatory T (Treg) cells has rendered the Th1/Th2 balance paradigm more complex and expanded our understanding of the pathogenesis of AR. IL-17, a key cytokine produced by Th17 cells, is known to induce allergen-specific Th2 cell activation, eosinophil and neutrophil accumulation, and serum IgE production in asthma; all of these features may play important roles in AR. To the best of our knowledge, only a few studies have assessed the feasibility of using IL-17 antagonists to treat AR. Thus, the principal objectives of the present study were, first, to determine the status of Th17 and Treg cells in the nasal mucosa of a mouse model of AR, and, second, to investigate the effects of IL-17 on such cells and the therapeutic efficacy of anti-IL-17 antibodies (Abs) in the context of AR. Anti-IL-17 Abs were given intranasally during the re-challenge of BALB/c mice with ovalbumin (OVA)-induced AR. We measured the numbers of nasal rubbing motions and sneezes, eosinophil and neutrophil levels, Th1, Th2, Th17, and Treg parameters in the nasal mucosa. Anti-IL-17 Abs markedly reduced the number of nasal rubbing motions and sneezes, decreased eosinophil and neutrophil infiltration, reduced Th2 and Th17 responses, and increased the Treg response. Anti-IL-17 Ab treatment protects against AR. These results will improve our understanding of AR pathogenesis and may lead to the development of novel therapeutic approaches for management of the condition.

A novel independent Th-cell subset, characterized by high expression of interleukin (IL)-9, has been recognized as the Th9 subset. Although Th9 cells are important in many diseases, their contribution to allergic rhinitis (AR) remains unclear. We therefore first determined whether Th9 cells were present in a mouse model of AR. We then investigated the their involvement in the distribution of CD4+ T-cell subsets and the symptoms of AR by treating mice with anti-IL-9 antibodies (Abs). Anti-IL-9 Abs were administered intranasally during rechallenge of ovalbumin (OVA)-induced AR in BALB/c mice. We measured nasal rubbing motion, sneezing and eosinophils, as well as the Th1 (Th1 cell percentage, Ifn-? mRNA/protein, T-bet mRNA), Th2 (Th2 cell percentage, Il-4 mRNA/protein, Gata3 mRNA), Th9 (Th9 cell percentages Il-9 mRNA/protein, PU.1 and Irf4 mRNA), Th17 (Th17 cell percentage, Il-17 mRNA/protein, Ror?t mRNA), and Treg (Treg cell percentage, Foxp3 mRNA) responses in the nasal mucosa. Treatment with anti-IL-9 Abs markedly reduced nasal rubbing, sneezing, eosinophil infiltration, and Th2, Th9, and Th17 responses, and increased the Treg response. Our findings emphasize the importance of IL-9/Th9 in the pathogenesis of AR, and suggest that anti-IL-9 Ab treatment may be an effective therapeutic strategy for AR.

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