Abstract
Fucosylation is a biological process that plays a critical role in multiple cellular functions from cell adhesion to immune regulation. Fucosyltransferases (FUTs) mediate fucosylation, and dysregulation of genes encoding FUTs is associated with various diseases. FUT1 and its fucosylated products are expressed in the ocular surface and ocular adnexa; however, the role of FUT1 in the ocular surface health and disease is yet unclear. Here, we investigated the effects of FUT1 on the ocular surface in steady-state conditions with age and under desiccating stress using a Fut1 knockout (KO) mouse model. We found that corneal epithelial defects and stromal opacity developed in Fut1 KO mice. Also, inflammatory responses in the ocular surface and Th1 cell activation in ocular draining lymph nodes (DLNs) were upregulated. Desiccating stress further aggravated Th1 cell-mediated immune responses in DLNs, lacrimal gland, and ocular surface in Fut1 KO mice, leading to severe corneal epithelial disruption and opacity. Mixed lymphocyte reaction assays revealed that the activity of splenocytes to stimulate CD4 T-cell proliferation was increased in Fut1 KO mice. Together, these data demonstrate that FUT1 deficiency induces immune dysregulation in the ocular surface and corneal opacity in steady state and under desiccating stress.
Highlights
Glycans are involved in a wide variety of physiologic and pathologic processes in eukaryotic cells after attachment to proteins or lipids through an enzymatic process called glycosylation[1]
H2 antigen are constitutively expressed in the ocular surface and lacrimal glands, and FUT1 deficiency leads to the ocular surface inflammation, corneal epithelial defects, and corneal opacification both in steady state and under desiccating stress
Th1 immune response was activated in the ocular surface, intraorbital lacrimal gland, and draining lymph nodes (DLNs) in FUT1-deficient mice
Summary
Glycans are involved in a wide variety of physiologic and pathologic processes in eukaryotic cells after attachment to proteins or lipids through an enzymatic process called glycosylation[1]. Fucosylated carbohydrates play an important role in the regulation of multiple cellular functions such as cell trafficking, immune cell development, and interaction with gut microbes and are generated through fucosylation mediated by fucosyltransferases (FUTs)[2,3,4]. 13 FUT genes have been identified in human genome based on their acceptor specificities and protein sequences[5]. Previous studies have demonstrated that FUT1 mediates diverse biologic processes by inducing angiogenesis and macrophage polarization in rheumatoid arthritis[8,9,10], promoting keratinocyte migration[11], and increasing cancer cell survival in breast and liver cancers[12,13]. A previous study showed that topical application of fucose accelerated corneal epithelial wound healing in a rabbit model of iodine vapor-induced corneal burn[17].
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