Acute and chronic lung inflammation drives changes in epithelial glycans

Frontiers in Immunology

Immunology

Brian A. Cobb¹  Kalob M. Reynero¹  Leandre M. Glendenning¹  Emily N. Kukan¹  Carlos A. Alvarez¹  Emily Qian² 

[1] Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, United States;Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, United States;Hathaway Brown High School, Beachwood, OH, United States;

关键词: asthma;    epithelium;    glycobiology;    inflammation;    lung;    mouse;   

DOI  :  10.3389/fimmu.2023.1167908

 received in 2023-02-16, accepted in 2023-05-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionAsthma is the most common chronic inflammatory disease and it is characterized by leukocyte infiltration and tissue remodeling, with the latter generally referring to collagen deposition and epithelial hyperplasia. Changes in hyaluronin production have also been demonstrated, while mutations in fucosyltransferases reportedly limit asthmatic inflammation. MethodsGiven the importance of glycans in cellular communication and to better characterize tissue glycosylation changes associated with asthma, we performed a comparative glycan analysis of normal and inflamed lungs from a selection of murine asthma models.ResultsWe found that among other changes, the most consistent was an increase in fucose-α1,3-N-acetylglucosamine (Fuc-α1,3-GlcNAc) and fucose-α1,2-galactose (Fuc-α1,2-Gal) motifs. Increases in terminal galactose and N-glycan branching were also seen in some cases, whereas no overall change in O-GalNAc glycans was observed. Increased Muc5AC was found in acute but not chronic models, and only the more human-like triple antigen model yielded increased sulfated galactose motifs. We also found that human A549 airway epithelial cells stimulated in culture showed similar increases in Fuc-α1,2-Gal, terminal galactose (Gal), and sulfated Gal, and this matched transcriptional upregulation of the α1,2-fucosyltransferase Fut2 and the α1,3-fucosyltransferases Fut4 and Fut7.ConclusionsThese data suggest that airway epithelial cells directly respond to allergens by increasing glycan fucosylation, a known modification important for the recruitment of eosinophils and neutrophils.

【 授权许可】

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Copyright © 2023 Alvarez, Qian, Glendenning, Reynero, Kukan and Cobb