Table 1.

Abnormal core fucosylation in gastrointestinal diseases

Types of immune modulation	Mechanism	Patterns of modulation	Disease	Ref.
Core fucosylation on gastrointestinal cellular immune modulation	Core fucosylation modulated T cell activation via TCR	Higher core fucosylation level existed in the sera of SLE patients and related to the severity of SLE. Increased core fucosylation in SLE patients was also correlated with CD4+ T cell activation	SLE	[51,53]
	Core fucosylation modulated TLRs recognition and signaling in macrophages	Core fucose was essential for CD14- dependent TLR4 and TLR2 signaling in murine macrophage activity, leading to DSS-induced experimental colitis	DSS-induced experimental colitis	[67]
Core fucosylation on gastrointestinal humoral immune modulation	Core fucosylation modulated humoral immune response	Loss of core fucosylation suppressed the humoral immune response in S. Typhi infection and resulted in suppressed sIgA production, which led to increased susceptibility to pathogens	S. Typhi infection	[70]
Core fucosylation on gastrointestinal tumor immune modulation	Core fucosylation modulated EMT	Caveolin-1 (Cav-1) could activate Wnt/β-catenin signaling to promote Fut8 expression which led to the proliferation and invasion of HCC	HCC	[97]
		Fut8 was a driver for the progress of hepatocyte growth factor (HGF)-induced EMT which was partially blocked by the silencing of Fut8 in HCC cells	HCC	[98]
		Core fucosylation on FOLR1 could enhance the folate uptake capacity to finally promote the EMT progress of HCC cells	HCC	[98]
		The low molecular weight population of E-cadherin was significantly increased after overexpression of Fut8, which resulted in an enhancement in cell–cell adhesion	Colorectal cancer	[99]
	Core fucosylation modulated EGFR and HGFR and biological functions	De-core fucosylation attenuated responses to EGF and HGF and blocked the EGF-induced phosphorylation of the EGFR in hepatocellular carcinoma	HCC	[37]
	Core fucosylation modulated PI3K-AKT-NF-κB signal pathway	HCV infection induced Fut8 expression to promote hepatocellular carcinoma proliferation by activating PI3K-AKT-NF-κB signaling	HCC	[113]
	Core fucosylation modulated cancerous radio-resistance	Fut8 inhibition increased the radiosensitivity of radioresistant ESCC cells and suppressed the growth and formation of tumors	ESCC	[119]
	Modulation of core fucosylation via microRNA, long non-coding RNA, and circular RNAs	LEF1-AS1 (lncRNA) silence hindered the tumorigenesis, and lung and liver metastasis of colon cancer cells in vivo, while overexpressed Fut8 abolished the suppressive impact of LEF1-AS1 repression on the biological behavior of colorectal cancer cells	Colorectal cancer	[121]
		MiR-198 targeted the 3'UTR of Fut8 directly to downregulate Fut8 expression at both mRNA and protein levels and suppressed the proliferation and invasion of colorectal carcinoma	Colorectal cancer	[122]
		MiR-122 and miR-34a were downregulated in spontaneous human hepatocarcinoma which could specifically interact with and regulate the 3'UTR of Fut8	HCC	[123]
		MiR-122-5p inhibited the expression of Fut8 and suppressed the proliferation and migration ability of the intrahepatic cholangiocarcinoma cell line via PI3K/AKT signaling pathway	Intrahepatic cholangiocarcinoma	[124]
		CircRNA cFUT8 promoted HCC development by binding free miR-548c and inhibiting the miR-548c/FUT8 regulatory axis	HCC	[126]

Mechanisms and patterns of different types of gastrointestinal immune modulation included cellular, humoral, and tumor immune modulation after modification with core fucosylation. The related diseases were also listed with the references. HCC: Hepatocellular cancer; EMT: Epithelial to mesenchymal transition; Fut8: Fucosyltransferase 8; CTL: Cytotoxic T cell; HCV: Hepatitis C virus; EGFR: Epidermal growth factor receptor; HGFR: Hepatocyte growth factor receptor; SLE: Systemic lupus erythematosus; ESCC: Esophageal squamous cell carcinoma. TLRs: Toll-like receptors; S. typhimurium: Salmonella typhimurium.