The protective role of conjunctival goblet cell mucin sialylation

Moe Matsuzawa, Tomoaki Ando (), Saaya Fukase, Meiko Kimura, Yasuharu Kume, Takuma Ide, Kumi Izawa, Ayako Kaitani, Mutsuko Hara, Eri Nakamura, Anna Kamei, Akira Matsuda, Nobuhiro Nakano, Keiko Maeda, Norihiro Tada, Hideoki Ogawa, Ko Okumura, Akira Murakami, Nobuyuki Ebihara and Jiro Kitaura ()
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Moe Matsuzawa: Juntendo University Graduate School of Medicine
Tomoaki Ando: Juntendo University Graduate School of Medicine
Saaya Fukase: Juntendo University Graduate School of Medicine
Meiko Kimura: Juntendo University Graduate School of Medicine
Yasuharu Kume: Juntendo University Graduate School of Medicine
Takuma Ide: Juntendo University Graduate School of Medicine
Kumi Izawa: Juntendo University Graduate School of Medicine
Ayako Kaitani: Juntendo University Graduate School of Medicine
Mutsuko Hara: Juntendo University Graduate School of Medicine
Eri Nakamura: Juntendo University Graduate School of Medicine
Anna Kamei: Juntendo University Graduate School of Medicine
Akira Matsuda: Juntendo University Graduate School of Medicine
Nobuhiro Nakano: Juntendo University Graduate School of Medicine
Keiko Maeda: Juntendo University Graduate School of Medicine
Norihiro Tada: Juntendo University Graduate School of Medicine
Hideoki Ogawa: Juntendo University Graduate School of Medicine
Ko Okumura: Juntendo University Graduate School of Medicine
Akira Murakami: Juntendo University Graduate School of Medicine
Nobuyuki Ebihara: Juntendo University Urayasu Hospital
Jiro Kitaura: Juntendo University Graduate School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Gel-forming mucins secreted by conjunctival goblet cells have been implicated in the clearance of allergens, pathogens, and debris. However, their roles remain incompletely understood. Here we show that human and mouse conjunctival goblet cell mucins have Alcian blue-detectable sialic acids, but not sulfates in the steady state. Interestingly, Balb/c mouse strain lacks this sialylation due to a point mutation in a sialyltransferase gene, St6galnac1, which is responsible for sialyl-Tn synthesis. Introduction of intact St6galnac1 to Balb/c restores the sialylation of conjunctival goblet cell mucus. Sialylated mucus efficiently captures and encapsulates the allergen particles in an impenetrable layer, leading to the protection of mice from the development of allergic conjunctivitis. Expression of ST6GALNAC1 and sialyl-Tn is upregulated in humans under conditions with chronic stimuli. These results indicate that the sialylated glycans on the ocular mucins play an essential role in maintaining the conjunctival mucosa by protecting from the incoming foreign bodies such as allergen particles.

Date: 2023
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DOI: 10.1038/s41467-023-37101-y

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