CD4⁺ T cell activation promotes the pathogenic process of systemic lupus erythematosus (SLE). T cell receptor (TCR) complex are highly core fucosylated glycoproteins, which play important roles in T cell activation. In this study, we found that the core fucosylation of CD4⁺ T cells was significantly increased in SLE patients. Loss of core fucosyltransferase (Fut8), the sole enzyme for catalyzing the core fucosylation of N-glycan, significantly reduced CD4⁺ T cell activation and ameliorated the experimental autoimmune encephalomyelitis-induced syndrome in Fut8^−/− mice. T cell activation with OVA_323–339 loaded major histocompatibility complex II (pMHC-II) on B cell was dramatically attenuated in Fut8^−/−OT-II CD4⁺ T cells compared with Fut8^+/+OT-II CD4⁺ T cells. Moreover, the phosphorylation of ZAP-70 was significantly reduced in Fut8^+/+OT-II CD4⁺ T cells by the treatment of fucosidase. Our results suggest that core fucosylation is required for efficient TCR–pMHC-II contacts in CD4⁺ T cell activation, and hyper core fucosylation may serve as a potential novel biomarker in the sera from SLE patients.

Vaginal dysbiosis often occurs in patients with cervical cancer. The fucosylation of mucosal epithelial cells is closely related to microbial colonization, and play an important role in protecting the vaginal mucosal epithelial cells. However, no reports on the relationship between vaginal dysbiosis and abnormal mucosal epithelial cell fucosylation, and their roles in the occurrence and development of cervical cancer are unavailable. Here we report that core fucosylation levels were significantly lower in the serum, exfoliated cervical cells and tumor tissue of cervical cancer patients. Core fucosyltransferase gene (Fut8) knockout promoted the proliferation and migration of cervical cancer cells. In patients with cervical cancer, the vaginal dysbiosis, and the abundance ofLactobacillus, especiallyL. iners, was significantly reduced. Meanwhile, the abundance ofL.inerswas positively correlated with core fucosylation levels. TheL. inersmetabolite lactate can activate the Wnt pathway through the lactate-Gpr81 complex, which increases the level of core fucosylation in epidermal cells, inhibiting the proliferation and migration of cervical cancer cells, and have application prospects in regulating the vaginal microecology and preventing cervical cancer.

The maternal milk glycobiome is crucial for shaping the gut microbiota of infants. Although high core fucosylation catalyzed by fucosyltransferase 8 (Fut8) is a general feature of human milk glycoproteins, its role in the formation of a healthy microbiota has not been evaluated. In this study, we found that the core-fucosylated N-glycans in milk of Chinese mothers selectively promoted the colonization of specific gut microbial groups, such as Bifidobacterium spp. and Lactobacillus spp. in their breast-fed infants during lactation. Compared with Fut8^+/+ (WT) mouse-fed neonates, the offspring fed by Fut8^+/− maternal mice had a distinct gut microbial profile, which was featured by a significant reduction of Lactobacillus spp., Bacteroides spp., and Bifidobacterium spp. and increased abundance of members of the Lachnospiraceae NK4A136 group and Akkermansia spp. Moreover, these offspring mice showed a lower proportion of splenic CD19⁺ CD69⁺ B lymphocytes and attenuated humoral immune responses upon ovalbumin (OVA) immunization. In vitro studies demonstrated that the chemically synthesized core-fucosylated oligosaccharides possessed the ability to promote the growth of tested Bifidobacterium and Lactobacillus strains in minimal medium. The resulting L-fucose metabolites, lactate and 1,2-propanediol, could promote the activation of B cells via the B cell receptor (BCR)-mediated signaling pathway. IMPORTANCE This study provides novel evidence for the critical role of maternal milk protein glycosylation in shaping early-life gut microbiota and promoting B cell activation of neonates. The special core-fucosylated oligosaccharides might be promising prebiotics for the personalized nutrition of infants.