IL-33, but Not IL-25, Is Crucial for the Development of House Dust Mite Antigen-Induced Allergic Rhinitis

Wakako Nakanishi,Hirohisa Saito,Kenji Matsumoto,Susumu Nakae,Akiko Shibui,Hajime Suto,Aya Nambu,Akira Matsuda,Sachiko Yamaguchi,Kenji Kondo,Maho Suzukawa,Tatuya Yamasoba,Cordula M Stover

doi:10.1371/journal.pone.0078099

Abstract

Both interleukin (IL)-33 and IL-25 induce Th2 cytokine production by various cell types, suggesting that they contribute to development of allergic disorders. However, the precise roles of IL-33 and IL-25 in house dust mite (HDM)-induced allergic rhinitis (AR) remain unclear. Both IL-33 and IL-25 were produced mainly by nasal epithelial cells during HDM-induced AR. Eosinophil and goblet cell counts in the nose and IL-5 levels in lymph node cell culture supernatants were significantly decreased in IL-33-deficient, but not IL-25-deficient, mice compared with wild-type mice during HDM-induced AR, but the serum IgE and IgG1 levels did not differ. On the other hand, HDM-induced AR developed similarly in wild-type mice transferred with either IL-33-deficient BM cells or wild-type BM cells. IL-33, but not IL-25, produced by nasal epithelial cells was crucial for the development of murine HDM-induced AR. These observations suggest that IL-33 neutralization may be a potential approach for treatment of HDM-induced AR in humans.

Highlights

Allergic rhinitis (AR) is roughly divided into intermittent AR and persistent/perennial AR [1]
These findings suggest that IL-25 and IL-33 may somehow contribute to the development of house dust mites (HDM)-induced AR
The numbers of eosinophils and goblet cells in the nasal mucosa were significantly reduced in IL-332/2 mice compared with wild-type mice 48 hours after the last inhalation of HDM extract (Figure. 3B), the thickness of the submucosal layers was comparable between these groups (Figure. 3B)

Summary

Introduction

Allergic rhinitis (AR) is roughly divided into intermittent (seasonal) AR (such as pollinosis) and persistent/perennial AR [1]. AR_ENREF_1 is considered to be a Th2 cytokine-mediated nasal inflammation that is accompanied by accumulation of eosinophils and mast cells in the nasal mucosa and increased serum levels of antigen-specific IgE [2]. IL33 potently induces production of Th2 cytokines such as IL-4, IL-5 and/or IL-13 by Th2 cells, mast cells, basophils, NKT cells and natural helper cells [7,8]. Similar to IL-33, IL-25 ( called IL17E) and TSLP—which are cytokines of the IL-17 family and the IL-7 family, respectively, and are preferentially produced by epithelial cells—can induce Th2 cytokine production by various types of cells, such as Th2 cells, NKT cells and natural helper cells, via IL-25R (composed of IL-17RA and IL-17R_ENREF_6B) and TSLPR (composed of IL-7Ra and TSLPR) [6,9,10,11]. Treatment of mice with exogenous IL-33, IL-25 or TSLP results in development of intestinal and/or pulmonary inflammation accompanied by accumulation of doi:10.1371/journal.pone.0078099.g001

Methods

Results

Conclusion