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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 2

Kinetics and cell populations for antigen uptake.

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Kinetics and cell populations for antigen uptake.
(A) Frequencies of the...
(A) Frequencies of the pooled dispersed conjunctival cell populations. Leu, leukocytes; Epi, epithelial cells; St, stromal cells. (B and C) Kinetics of the frequencies of indicated cell populations (B) and those of indicated cell populations that are OVA-AF647 positive (C) (n = 4, each time point). Data are shown as mean ± SEM (B and C). (D) Unsupervised clustering of the conjunctival cells. The expression levels of CD45 and EpCAM are shown in heatmaps. OVA-AF647–high cells are shown in blue. (E) Unsupervised clustering of the CD45+ cells revealed 7 distinct populations with differential forward- and side-scatter distributions. The expression levels of the indicated markers are shown in heatmaps. (F) Kinetics of OVA-AF647 uptake by the indicated cell populations (n = 4, each time point). B6 mice were used for all experiments.

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