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A nerve-goblet cell association promotes allergic conjunctivitis through rapid antigen passage
Meiko Kimura, Tomoaki Ando, Yasuharu Kume, Saaya Fukase, Moe Matsuzawa, Kosuke Kashiwagi, Kumi Izawa, Ayako Kaitani, Nobuhiro Nakano, Keiko Maeda, Hideoki Ogawa, Ko Okumura, Shintaro Nakao, Akira Murakami, Nobuyuki Ebihara, Jiro Kitaura
Meiko Kimura, Tomoaki Ando, Yasuharu Kume, Saaya Fukase, Moe Matsuzawa, Kosuke Kashiwagi, Kumi Izawa, Ayako Kaitani, Nobuhiro Nakano, Keiko Maeda, Hideoki Ogawa, Ko Okumura, Shintaro Nakao, Akira Murakami, Nobuyuki Ebihara, Jiro Kitaura
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Research Article Immunology Ophthalmology

A nerve-goblet cell association promotes allergic conjunctivitis through rapid antigen passage

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Abstract

The penetration of allergens through the epithelial layer is the initial step in the development of allergic conjunctivitis. Although pollinosis patients manifest symptoms within minutes after pollen exposure, the mechanisms of the rapid transport of the allergens remain unclear. In the present study, we found that the instillation of pollen shells rapidly induces a large number of goblet cell–associated antigen passages (GAPs) in the conjunctiva. Antigen acquisition by stromal cells, including macrophages and CD11b+ dendritic cells, correlated with surface GAP formation. Furthermore, a substantial amount of antigen was transported to the stroma during the first 10 minutes of pollen exposure, which was sufficient for the full induction of an allergic conjunctivitis mouse model. This inducible, rapid GAP formation and antigen acquisition were suppressed by topical lidocaine or trigeminal nerve ablation, indicating that the sensory nervous system plays an essential role. Interestingly, pollen shell–stimulated GAP formation was not suppressed by topical atropine, suggesting that the conjunctival GAPs and intestinal GAPs are differentially regulated. These results identify pollen shell–induced GAP as a therapeutic target for allergic conjunctivitis.

Authors

Meiko Kimura, Tomoaki Ando, Yasuharu Kume, Saaya Fukase, Moe Matsuzawa, Kosuke Kashiwagi, Kumi Izawa, Ayako Kaitani, Nobuhiro Nakano, Keiko Maeda, Hideoki Ogawa, Ko Okumura, Shintaro Nakao, Akira Murakami, Nobuyuki Ebihara, Jiro Kitaura

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Figure 1

Repeated topical application of OVA combined with RW pollen shells elicits eosinophilic conjunctivitis.

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Repeated topical application of OVA combined with RW pollen shells elici...
(A) Giemsa staining of the conjunctival tissue at ×200 magnification. Scale bars: 50 μm (lower magnification) and 10 μm (insets). Arrowheads denote eosinophils. (B–D) Conjunctival eosinophil populations among CD45+ cells (B and C) and cell numbers of indicated populations in the conjunctiva (D). Pooled results of 2 independent experiments (n = 8–18). Data are shown as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by 2-tailed Kruskal-Wallis test with Dunn’s multiple-comparison test. (E) Pearson’s correlation between CD4+ST2+ T cell and eosinophil numbers in the conjunctiva. The B6 mouse strain was used for all experiments.

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