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 3

RW pollen shells promote GAP formation and antigen uptake through the conjunctiva.

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RW pollen shells promote GAP formation and antigen uptake through the co...
(A) Localization of OVA-AF647 in the conjunctiva at the indicated time periods after topical instillation of RW pollen shells and OVA-AF647. (B) Representative morphology of GAPs in the conjunctiva. (C and D) GAP formation in the conjunctiva 5 minutes after instillation of the indicated formula. Representative images (C) and quantitation (D) (n = 4, each condition). *P < 0.05 by 2-tailed Mann-Whitney test. (E) Representative images of the conjunctival surface with the corresponding stroma below. Scale bars: 50 μm (lower magnification) and 10 μm (insets) (A–C and E). (F) Diagram for OVA-AF647 uptake experiment. Naive mice were challenged once, and the antigen uptake was evaluated. (G–I) Frequencies of OVA-AF647+ cells and mean fluorescence intensity (MFI) in the indicated cell populations (n = 2–8). A.U., arbitrary units; N, nontreated. The nontreated samples were used for setting the positive gate and were excluded from the statistical analysis. **P < 0.01 by 2-tailed Student’s t test with Welch’s correction. (J) Diagram of the antigen transport experiment. CLN, cervical lymph nodes. (K and L) Frequencies of OVA-AF647+ cells in the indicated populations in the cervical lymph nodes (n = 3–6). B6 mice were used for all experiments. Data are shown as mean ± SEM (D, H, I, and L).