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Updated: Jan 17, 2026

Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
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Trefoil factor 2 interacts with A4GNT to regulate inflammation to protect against pneumonia during influenza virus

Weihui Fu1, Jun Fan1, Tianyun Peng1

  • 1Shanghai Public Health Clinical Center, Zhongshan Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

Iscience
|September 25, 2025
PubMed

Insights

Trefoil factor 2 (TFF2) protects mice from pneumonia during influenza virus infection. This protective effect involves TFF2 binding to cell surface glycans via A4GNT, restraining inflammation and offering potential for respiratory disease treatments.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Trefoil factor 2 (TFF2) is known for its anti-inflammatory and mucosal repair properties in the gastrointestinal tract.
  • The role of TFF2 in acute respiratory tract infections, particularly influenza, is not well understood.

Purpose of the Study:

  • To investigate the protective role of TFF2 in mouse models of influenza virus-induced pneumonia.
  • To elucidate the molecular mechanism by which TFF2 exerts its protective effects.

Main Methods:

  • Influenza virus infection model in mice.
  • In vitro binding assays to identify TFF2 receptors.
  • Analysis of signaling pathways, including Src-family kinases (SFKs) phosphorylation.
  • Investigation of the TFF2-A4GNT-glycan complex.

Main Results:

  • TFF2 administration protected mice against pneumonia caused by influenza virus infection.
  • TFF2 binds to cell surface glycans through α1,4-N-acetylglucosaminyltransferase (A4GNT) activity, not previously identified receptors.
  • TFF2 forms a complex that restrains inflammation by augmenting inhibitory Src-family kinases (SFKs) phosphorylation (Tyr527) and preventing stimulatory phosphorylation (Tyr416).

Conclusions:

  • The protective effect of TFF2 against influenza pneumonia is mediated by the TFF2-A4GNT-glycan axis.
  • TFF2 represents a potential therapeutic target for acute respiratory inflammatory diseases.
Keywords:
Cell biologyMicrobiologyViral microbiology

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