Involvement of langerin in the protective function of a keratan sulfate-based disaccharide in an emphysema mouse model.

Publication date: Jul 14, 2023

Chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis, is now the third cause of death worldwide and COVID-19 infection has been reported as an exacerbation factor of them. In this study, we report that the intratracheal administration of the keratan sulfate-based disaccharide L4 mitigates the symptoms of an elastase-induced emphysema in a mouse model. To know the molecular mechanisms, we performed a functional analysis of a C-type lectin receptor, langerin, a molecule that binds L4. Using mouse BMDCs (bone marrow-derived dendritic cells) as langerin-expressing cells, we observed the downregulation of IL-6 and TNFa and the upregulation of IL-10 after incubation with L4. We also identified CapG (a macrophage-capping protein) as a possible molecule that binds langerin by immunoprecipitation combined with a mass spectrometry analysis. We identified a portion of the CapG that was localized in the nucleus and binds to the promoter region of IL-6 and the TNFa gene in BMDCs, suggesting that CapG suppresses the gene expression of IL-6 and TNFa as an inhibitory transcriptional factor. To examine the effects of L4 in in vivo, we also generated langerin-knockout mice by means of genome editing technology. In an emphysema mouse model, the administration of L4 did not mitigate the symptoms of emphysema as well as the inflammatory state of the lung in the langerin-knockout mice. These data suggest that the anti-inflammatory effect of L4 through the langerin-CapG axis represents a potential therapeutic target for the treatment of emphysema and COPD.

Concepts Keywords
Bone CapG
Bronchitis Carbohydrate function
Immunoprecipitation Dendritic cell
L4 Glycobiology
Mice Inflammation
Keratan sulfate


Type Source Name
disease MESH emphysema
disease MESH Chronic obstructive pulmonary disease
disease MESH chronic bronchitis
disease MESH cause of death
disease MESH COVID-19
disease MESH infection
disease VO report
drug DRUGBANK Interleukin-10
disease VO gene
disease IDO cell
disease MESH Inflammation

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