A nerve-goblet cell association promotes allergic conjunctivitis through rapid antigen passage
Meiko Kimura, … , Nobuyuki Ebihara, Jiro Kitaura
Meiko Kimura, … , Nobuyuki Ebihara, Jiro Kitaura
Published October 11, 2023
Citation Information: JCI Insight. 2023;8(21):e168596. https://doi.org/10.1172/jci.insight.168596.
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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 6

Muscarinic acetylcholine receptors (mAchRs) are not essential for RW pollen shell–stimulated GAP formation.

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Muscarinic acetylcholine receptors (mAchRs) are not essential for RW pol...
(A) mAchRs are stimulated by carbamylcholine (CCh) and inhibited by atropine (Atr). (B) Kinetics of mydriasis after atropine instillation. (C and D) GAP formation 5 minutes after instillation of OVA-AF647 and pollen shells. The indicated formula was instilled 30 minutes prior to the challenge. Representative image (C) and quantification (D) (n = 6, each). Scale bar: 50 μm. (E) Diagram of the antigen passage experiment. Sal, saline. (F and G) The frequencies of OVA-AF647+ cells (F) and the mean fluorescence intensity (MFI) (G) of the indicated cell types (n = 2–8). N, nontreated. (H) Kinetics of miosis after CCh instillation to the euthanized mice (n = 3, each). *P < 0.05 by 2-way ANOVA with Holm-Šidák multiple-comparison test. (I and J) GAP formation and mucus secretion after instillation of OVA-AF647 along with the indicated formula. Representative images (I) and GAP quantitation (J) (n = 6–8). Scale bars: 50 μm (lower magnification) and 10 μm (insets). Annotated diagrams of the goblet cells in the insets are also shown. (K) Diagram for the antigen passage experiment in L and M. (L and M) The frequencies of OVA-AF647+ cells (L) and the MFI (M) of the indicated cell types. The nontreated samples were used for setting the positive gate and were excluded from the statistical analysis. *P < 0.05, **P < 0.01 by 1-way ANOVA with Holm-Šidák multiple-comparison test (L) and Kruskal-Wallis test with Dunn’s multiple-comparison test (M) against saline- and OVA-AF647–treated mice (n = 2–8). In L and M, (–) indicates no treatment. Data are shown as mean ± SEM (B, D, F–H, J, L, and M). B6 mice were used for all the experiments.