Hyper α2,6‐Sialylation Promotes CD4+ T‐Cell Activation and Induces the Occurrence of Ulcerative Colitis
Abstract α2,6‐sialylation, catalyzed by α2,6‐sialyltransferase (ST6GAL1), plays a pivotal role in immune responses. However, the role of ST6GAL1 in the pathogenesis of ulcerative colitis (UC) remains unknown. ST6GAL1 mRNA is highly expressed in UC tissues compared with the corresponding adjacent nor...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202302607 |
| _version_ | 1797684953552519168 |
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| author | Qingjie Fan Mechou Li Weiwei Zhao Kaixin Zhang Ming Li Wenzhe Li |
| author_facet | Qingjie Fan Mechou Li Weiwei Zhao Kaixin Zhang Ming Li Wenzhe Li |
| author_sort | Qingjie Fan |
| collection | DOAJ |
| description | Abstract α2,6‐sialylation, catalyzed by α2,6‐sialyltransferase (ST6GAL1), plays a pivotal role in immune responses. However, the role of ST6GAL1 in the pathogenesis of ulcerative colitis (UC) remains unknown. ST6GAL1 mRNA is highly expressed in UC tissues compared with the corresponding adjacent normal tissues, and α2,6‐sialylation is significantly increased in the colon tissues of patients with UC. The expression of ST6GAL1 and proinflammatory cytokines, such as interleukin (IL)‐2, IL‐6, IL‐17, and interferon‐gamma, is also increased. The number of CD4+ T cells increases in UC patients. St6gal1 gene knockout (St6gal1−/‐) rats are established by clustered regularly interspaced short palindromic repeats (CRISPR)‐associated gene knockout system. St6gal1 deficiency reduces the levels of pro‐inflammatory cytokines and alleviates colitis symptoms in UC model rats. Ablation of α2,6‐sialylation inhibits the transport of the TCR to lipid rafts and suppresses CD4+ T‐cell activation. The attenuation of TCR signaling downregulates the expression of NF‐κB in ST6GAL1‐/‐ CD4+ T‐cells. Moreover, NF‐κB could bind to the ST6GAL1 promoter to increase its transcription. Ablation of ST6GAL1 downregulates the expression of NF‐κB and reduces the production of proinflammatory cytokines to relieve UC pathogenesis, which is a potential novel target for the clinical treatment of UC. |
| first_indexed | 2024-03-12T00:37:20Z |
| format | Article |
| id | doaj.art-99f6e97e243341cca73104ae8b5b5a00 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-12T00:37:20Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-99f6e97e243341cca73104ae8b5b5a002023-09-15T09:28:59ZengWileyAdvanced Science2198-38442023-09-011026n/an/a10.1002/advs.202302607Hyper α2,6‐Sialylation Promotes CD4+ T‐Cell Activation and Induces the Occurrence of Ulcerative ColitisQingjie Fan0Mechou Li1Weiwei Zhao2Kaixin Zhang3Ming Li4Wenzhe Li5Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology Shantou University Medical College Shantou Guangdong 515041 ChinaCollege of Basic Medical Science Dalian Medical University 9‐Western Section, Lvshun South RoadDalian Liaoning 116044 ChinaCollege of Basic Medical Science Dalian Medical University 9‐Western Section, Lvshun South RoadDalian Liaoning 116044 ChinaCollege of Basic Medical Science Dalian Medical University 9‐Western Section, Lvshun South RoadDalian Liaoning 116044 ChinaCollege of Basic Medical Science Dalian Medical University 9‐Western Section, Lvshun South RoadDalian Liaoning 116044 ChinaGuangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology Shantou University Medical College Shantou Guangdong 515041 ChinaAbstract α2,6‐sialylation, catalyzed by α2,6‐sialyltransferase (ST6GAL1), plays a pivotal role in immune responses. However, the role of ST6GAL1 in the pathogenesis of ulcerative colitis (UC) remains unknown. ST6GAL1 mRNA is highly expressed in UC tissues compared with the corresponding adjacent normal tissues, and α2,6‐sialylation is significantly increased in the colon tissues of patients with UC. The expression of ST6GAL1 and proinflammatory cytokines, such as interleukin (IL)‐2, IL‐6, IL‐17, and interferon‐gamma, is also increased. The number of CD4+ T cells increases in UC patients. St6gal1 gene knockout (St6gal1−/‐) rats are established by clustered regularly interspaced short palindromic repeats (CRISPR)‐associated gene knockout system. St6gal1 deficiency reduces the levels of pro‐inflammatory cytokines and alleviates colitis symptoms in UC model rats. Ablation of α2,6‐sialylation inhibits the transport of the TCR to lipid rafts and suppresses CD4+ T‐cell activation. The attenuation of TCR signaling downregulates the expression of NF‐κB in ST6GAL1‐/‐ CD4+ T‐cells. Moreover, NF‐κB could bind to the ST6GAL1 promoter to increase its transcription. Ablation of ST6GAL1 downregulates the expression of NF‐κB and reduces the production of proinflammatory cytokines to relieve UC pathogenesis, which is a potential novel target for the clinical treatment of UC.https://doi.org/10.1002/advs.202302607α2,6‐sialylationlipid raftsnuclear factor‐κ‐gene bindingST6GAL1T‐cell receptorulcerative colitis |
| spellingShingle | Qingjie Fan Mechou Li Weiwei Zhao Kaixin Zhang Ming Li Wenzhe Li Hyper α2,6‐Sialylation Promotes CD4+ T‐Cell Activation and Induces the Occurrence of Ulcerative Colitis Advanced Science α2,6‐sialylation lipid rafts nuclear factor‐κ‐gene binding ST6GAL1 T‐cell receptor ulcerative colitis |
| title | Hyper α2,6‐Sialylation Promotes CD4+ T‐Cell Activation and Induces the Occurrence of Ulcerative Colitis |
| title_full | Hyper α2,6‐Sialylation Promotes CD4+ T‐Cell Activation and Induces the Occurrence of Ulcerative Colitis |
| title_fullStr | Hyper α2,6‐Sialylation Promotes CD4+ T‐Cell Activation and Induces the Occurrence of Ulcerative Colitis |
| title_full_unstemmed | Hyper α2,6‐Sialylation Promotes CD4+ T‐Cell Activation and Induces the Occurrence of Ulcerative Colitis |
| title_short | Hyper α2,6‐Sialylation Promotes CD4+ T‐Cell Activation and Induces the Occurrence of Ulcerative Colitis |
| title_sort | hyper α2 6 sialylation promotes cd4 t cell activation and induces the occurrence of ulcerative colitis |
| topic | α2,6‐sialylation lipid rafts nuclear factor‐κ‐gene binding ST6GAL1 T‐cell receptor ulcerative colitis |
| url | https://doi.org/10.1002/advs.202302607 |
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