{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CHST6 encodes a carbohydrate sulfotransferase enzyme that mediates the 6‐O‐sulfation of N‐acetylglucosamine residues on glycoproteins and proteoglycans. In airway epithelial cells, up‐regulation of CHST6 (along with other sulfotransferases) by inflammatory cytokines leads to an increased formation of terminal 6‐sulfo–sialyl Lewis x structures on mucins; these modified glycans serve as preferential binding sites for pathogens such as "}, {"type": "i", "children": [{"type": "t", "text": "Pseudomonas aeruginosa"}]}, {"type": "t", "text": " in cystic fibrosis, thereby potentially contributing to the chronicity of airway infections."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the cornea, CHST6 plays a central role in sulfating keratan sulfate, a key component of the extracellular matrix that is crucial for maintaining corneal transparency and biomechanical integrity. Loss‐of‐function mutations in CHST6, whether through missense, nonsense, frameshift, or deletion events, lead to the production of unsulfated or aberrantly sulfated glycosaminoglycans and are responsible for the pathogenesis of macular corneal dystrophy (MCD)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " A wide allele heterogeneity has been documented in different populations, with a spectrum of mutations leading to variable immunophenotypes of MCD; such genetic diversity underscores the enzyme’s indispensable role in regulating the sulfation pattern of keratan sulfate and its contribution to corneal structure and clarity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, altered CHST6 expression and function have been linked to cellular changes—including endoplasmic reticulum stress, modified cell migration, and senescence—in corneal stromal cells, which may further impact corneal biosynthesis and tissue engineering strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Collectively, these findings highlight CHST6 as a pivotal enzyme in the posttranslational modification of glycan structures that is essential for both the proper function of airway mucins and the maintenance of corneal transparency; its dysfunction due to genetic alterations not only drives MCD pathology but also represents a potential target for therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sophie Groux-Degroote, Marie-Ange Krzewinski-Recchi, Aurélie Cazet, et al. 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