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

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 4

Early antigen passage is essential for the antigen uptake and the development of allergic conjunctivitis.

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Early antigen passage is essential for the antigen uptake and the develo...
(A) Experimental diagram for panels B and C. (B and C) The frequencies of OVA-AF647+ cells (B) and the mean fluorescence intensity (MFI) (C) of the indicated cell populations in the conjunctiva that was exposed to OVA-AF647 with RW pollen shells for the indicated periods of time (n = 2–6). A.U., arbitrary units; N, nontreated. The nontreated samples were used for setting the positive gate and were excluded from the statistical analysis. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 by 2-tailed Brown-Forsythe and Welch’s ANOVA test with Dunnett’s T3 multiple-comparison test against the 30-minute exposure. (D) Experimental diagram for panels E and F. Naive mice were challenged once, and the antigen uptake was evaluated. (E and F) The antigen uptake by indicated cell types after instillation of the indicated formula (n = 2–8). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by 2-tailed Student’s t test with Welch’s correction. (G) Experimental diagram of the systemically sensitized model of allergic conjunctivitis with eye wash at the indicated time points after instillation of pollen suspension. (H) Representative gating of eosinophil populations among CD45+ cells. (I and J) Cell numbers of indicated populations (I) and their correlation (J) (n = 3–5). Sal, saline. In I, (–) indicates no treatment. Data are shown as mean ± SEM (B, C, E, F, and I). *P < 0.05, **P < 0.01 by Kruskal-Wallis test with Dunn’s multiple-comparison test against saline-challenged mice. B6 mice were used for A–F and BALB/c mice were used for G–J.