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FUT1 deficiency elicits immune dysregulation and corneal opacity in steady state and under stress.


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.

SUBMITTER: Kim KW 

PROVIDER: S-EPMC7181665 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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FUT1 deficiency elicits immune dysregulation and corneal opacity in steady state and under stress.

Kim Kyoung Woo KW   Ryu Jin Suk JS   Ko Jung Hwa JH   Kim Jun Yeob JY   Kim Hyeon Ji HJ   Lee Hyun Ju HJ   Oh Jang-Hee JH   Chung Jin Ho JH   Oh Joo Youn JY  

Cell death & disease 20200424 4


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 i  ...[more]

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