Interleukin-33 and thymic stromal lymphopoietin, but not interleukin-25, are crucial for development of airway eosinophilia induced by chitin

Ken Arae,Kenji Matsumoto,Haruhiko Taguchi,Hideaki Morita,Ko Okumura,Hirohisa Saito,Youji Okada,Hajime Suto,Susumu Nakae,Kotaro Horiguchi,Keisuke Orimo,Sachiko Yamaguchi,Masashi Ikutani,Hiroki Sugiyama,Katsuko Sudo

doi:10.1038/s41598-021-85277-4

Abstract

Exposure to various antigens derived from house dust mites (HDM) is considered to be a risk factor for development of certain allergic diseases such as atopic asthma, atopic dermatitis, rhinitis and conjunctivitis. Chitin is an insoluble polysaccharide (β-(1–4)-poly-N-acetyl-d-glucosamine) and a major component in the outer shell of HDMs. Mice exposed to chitin develop asthma-like airway eosinophilia. On the other hand, several lines of evidence show that the effects of chitin on immune responses are highly dependent on the size of chitin particles. In the present study, we show that chitin induced production of IL-33 and TSLP by alveolar and bronchial epithelial cells, respectively, in mice. IL-25, IL-33 and TSLP were reported to be important for group 2 innate lymphoid cell (ILC2)-, but not Th2 cell-, dependent airway eosinophilia in a certain model using chitin beads. Here, we show that—in our murine models—epithelial cell-derived IL-33 and TSLP, but not IL-25, were crucial for activation of resident lung Th2 cells as well as group 2 innate lymphoid cells (ILC2s) to produce IL-5, resulting in development of chitin-induced airway eosinophilia. Our findings provide further insight into the underlying mechanisms of development of HDM-mediated allergic disorders.

Highlights

Exposure to various antigens derived from house dust mites (HDM) is considered to be a risk factor for development of certain allergic diseases such as atopic asthma, atopic dermatitis, rhinitis and conjunctivitis
Several lines of evidence show that the effects of chitin on immune responses are highly dependent on the size of chitin particles[19,20,21]
The leukocyte profiles in the bronchoalveolar lavage (BAL) fluids were similar with 100 μg of chitin in all sizes (Fig. 1b), the numbers of neutrophils and eosinophils in BAL fluids from mice treated with the large size (70–100 μm) of chitin were significantly larger than those with the small size (< 40 μm) of chitin (p < 0.05)

Summary

Introduction

Exposure to various antigens derived from house dust mites (HDM) is considered to be a risk factor for development of certain allergic diseases such as atopic asthma, atopic dermatitis, rhinitis and conjunctivitis. We show that—in our murine models—epithelial cell-derived IL-33 and TSLP, but not IL-25, were crucial for activation of resident lung Th2 cells as well as group 2 innate lymphoid cells (ILC2s) to produce IL-5, resulting in development of chitin-induced airway eosinophilia. Papain activates pulmonary epithelial cells to produce IL-33, which can induce type 2 cytokines This results in development of type 2 cytokine-dependent airway eosinophilia through activation of group 2 innate lymphoid cells (ILC2s) and basophils, even in the absence of adaptive immune c ells[12,13,14,15]. In addition to protease allergens, exposure to chitin, which is an insoluble polysaccharide (β-(1–4)-polyN-acetyl-d-glucosamine) and a major component in the outer shell of HDMs, can lead to development of asthma-like airway eosinophilia through activation of innate immune cells, even in the absence of adaptive immune cells[16]. We investigated the effects of different sizes of chitin particles on chitin-mediated airway eosinophilia in mice

Methods

Results

Conclusion