Glycosylation is a fundamental post-translational modification that regulates protein folding, stability, and cellular communication. Within glycan modifications, fucosylation—the addition of fucose residues mediated by fucosyltransferases (FUTs)—plays roles in immune regulation, epithelial homeostasis, and host–pathogen interactions. Because the respiratory mucosa depends on precise glycoprotein function for barrier and mucociliary roles, changes in glycosylation patterns, including fucosylation, are biologically plausible contributors to airway disease.
The review frames FUT biology in the context of airway pathophysiology and positions fucosylation as a modulator of multiple processes relevant to asthma: epithelial integrity, mucus properties, immune-cell interactions, inflammatory signaling, remodeling, and senescence.
Accumulating studies indicate that dysregulated fucosylation is associated with chronic inflammatory airway diseases such as asthma. Asthma is characterized by chronic airway inflammation, epithelial barrier dysfunction, mucus hypersecretion, and airway remodeling. Altered glycosylation patterns have been reported in these pathological processes, and specific changes in fucosylation have been implicated in mechanisms that could exacerbate or perpetuate airway disease.
The authors emphasize that while there is growing evidence linking FUT activity to disease-relevant phenotypes, direct mechanistic confirmation in human asthma is limited. Many insights come from experimental models or related respiratory conditions rather than definitive asthma-specific mechanistic studies.
Specific FUT isoforms are reported to regulate epithelial integrity. The airway epithelium forms a selective barrier and participates in immune signaling; its dysfunction is a hallmark of asthma. Altered fucosylation of cell-surface and secreted glycoproteins can influence cell–cell and cell–matrix interactions that maintain barrier function.
The review notes that FUT-dependent modifications may affect epithelial homeostasis through regulation of glycoprotein folding, stability, and interactions, thereby contributing to barrier disruption observed in asthma. However, the authors also clarify that direct proof linking particular FUT isoforms to epithelial barrier failure in human asthma remains incomplete and often extrapolated from model systems.
Mucus hypersecretion and changes in mucus composition are central features of asthma. FUTs can alter mucin glycosylation patterns, which may modify mucin physical properties, clearance, and interactions with microbes and immune mediators.
The review synthesizes evidence that FUT-driven fucosylation of mucins influences mucus characteristics relevant to obstruction and host defense. Nonetheless, the authors caution that many mechanistic details—such as which FUT isoforms drive clinically relevant mucin changes in asthma patients—are still unresolved.
Fucosylation influences immune regulation and cell trafficking. The review highlights data linking FUT activity to immune-cell recruitment and inflammatory signaling cascades implicated in asthma pathogenesis.
By modifying glycan ligands and receptors on epithelial or immune cells, FUTs may shape chemokine interactions, leukocyte adhesion, and downstream inflammatory responses. The authors differentiate between established associations and hypotheses derived from experimental models, underscoring the need for human-focused mechanistic work to confirm these pathways in asthma.
Emerging evidence suggests that FUT-mediated fucosylation could contribute to airway remodeling and cellular senescence—processes implicated in chronic asthma progression. The review discusses potential mechanisms whereby altered glycosylation affects extracellular matrix interactions, cell phenotype switching, and senescence-associated signaling.
However, the review explicitly notes that direct evidence for FUT-driven remodeling and senescence in asthma is limited. Many proposed links are drawn from related respiratory diseases or preclinical models rather than validated in human asthma cohorts.
Given the associations between fucosylation and multiple asthma-relevant pathways, FUTs are proposed as candidate sources for biomarker discovery and as potential targets for precision therapies. Altered glycan signatures or specific FUT expression profiles might inform disease phenotyping or therapeutic stratification.
The authors present this potential cautiously: while FUT-targeted strategies are conceptually promising, translational development requires clearer mechanistic validation, identification of specific isoforms of interest, and demonstration of clinical relevance in asthma populations.
The review highlights several challenges to progress in this area: limited direct mechanistic data in human asthma; reliance on findings from related respiratory diseases or animal/experimental models; and a need for refined glycoproteomic methods to map FUT-specific modifications in airway tissues and secretions.
Future research directions proposed include focused studies to identify which FUT isoforms are altered in asthma, mechanistic experiments to link specific fucosylation changes to epithelial dysfunction and immune responses, and translational work to evaluate FUT-related biomarkers and therapeutic interventions. The authors call for distinguishing established asthma-specific findings from emerging mechanistic hypotheses as the field advances.
Declarations reported in the source: ethical approval not applicable; the authors declared no conflict of interest.