tetano
Editor, Senior Moderator
iScience
. 2025 Aug 14;28(9):113370.
doi: 10.1016/j.isci.2025.113370. eCollection 2025 Sep 19. Trefoil factor 2 interacts with A4GNT to regulate inflammation to protect against pneumonia during influenza virus infection
Weihui Fu[SUP] 1 [/SUP], Jun Fan[SUP] 1 [/SUP], Tianyun Peng[SUP] 1 [/SUP], Peng Sun[SUP] 1 [/SUP], Songhua Yuan[SUP] 1 [/SUP], Cuisong Zhu[SUP] 1 [/SUP], Longfei Ding[SUP] 1 [/SUP], Linxia Zhang[SUP] 1 [/SUP], Chen Zhao[SUP] 1 [/SUP], Shuye Zhang[SUP] 1 [/SUP], Xiaoyan Zhang[SUP] 1 [/SUP], Jianqing Xu[SUP] 1 [/SUP]
Affiliations
Trefoil factor 2 (TFF2) has been shown to reduce inflammation and promote mucosal repair in models of gastric and colonic injury. However, the role of TFF2 in acute respiratory tract infection remains elusive. Here, we demonstrate that TFF2 protects mice against pneumonia in influenza virus infections. In vitro studies have revealed that TFF2 does not directly bind to the previously reported potential receptors but recognizes the terminal GlcNAc-α-1,4-Gal disaccharide of cell surface proteins mediated by the glycosyltransferase activity of α1,4-N-acetylglucosaminyltransferase (A4GNT). Functionally, TFF2 organized membranous TFF2-A4GNT-glycan protein complex serves to restrain cellular inflammation pathways by augmenting inhibitory Tyr527 phosphorylation at the C-terminus of Src-family kinases (SFKs), thereby effectively preventing the phosphorylation of stimulatory SFKs Tyr416. Finally, we have conclusively verified that the protective effect of TFF2 relies on the TFF2-A4GNT-glycan axis during influenza virus infection. In the future, TFF2 may offer a potential intervention strategy for acute respiratory inflammatory diseases.
Keywords: Cell biology; Microbiology; Viral microbiology.
. 2025 Aug 14;28(9):113370.
doi: 10.1016/j.isci.2025.113370. eCollection 2025 Sep 19. Trefoil factor 2 interacts with A4GNT to regulate inflammation to protect against pneumonia during influenza virus infection
Weihui Fu[SUP] 1 [/SUP], Jun Fan[SUP] 1 [/SUP], Tianyun Peng[SUP] 1 [/SUP], Peng Sun[SUP] 1 [/SUP], Songhua Yuan[SUP] 1 [/SUP], Cuisong Zhu[SUP] 1 [/SUP], Longfei Ding[SUP] 1 [/SUP], Linxia Zhang[SUP] 1 [/SUP], Chen Zhao[SUP] 1 [/SUP], Shuye Zhang[SUP] 1 [/SUP], Xiaoyan Zhang[SUP] 1 [/SUP], Jianqing Xu[SUP] 1 [/SUP]
Affiliations
- PMID: 40995127
- PMCID: PMC12454342
- DOI: 10.1016/j.isci.2025.113370
Trefoil factor 2 (TFF2) has been shown to reduce inflammation and promote mucosal repair in models of gastric and colonic injury. However, the role of TFF2 in acute respiratory tract infection remains elusive. Here, we demonstrate that TFF2 protects mice against pneumonia in influenza virus infections. In vitro studies have revealed that TFF2 does not directly bind to the previously reported potential receptors but recognizes the terminal GlcNAc-α-1,4-Gal disaccharide of cell surface proteins mediated by the glycosyltransferase activity of α1,4-N-acetylglucosaminyltransferase (A4GNT). Functionally, TFF2 organized membranous TFF2-A4GNT-glycan protein complex serves to restrain cellular inflammation pathways by augmenting inhibitory Tyr527 phosphorylation at the C-terminus of Src-family kinases (SFKs), thereby effectively preventing the phosphorylation of stimulatory SFKs Tyr416. Finally, we have conclusively verified that the protective effect of TFF2 relies on the TFF2-A4GNT-glycan axis during influenza virus infection. In the future, TFF2 may offer a potential intervention strategy for acute respiratory inflammatory diseases.
Keywords: Cell biology; Microbiology; Viral microbiology.