Tff1, also known as trefoil factor family 1 or pS2, is a small secreted peptide. It has gastrointestinal protective functions, is involved in mucin polymerization, cell motility, proliferation and/or differentiation [2,4]. It may play a role in maintaining the integrity of the gastric mucosa and has been associated with various signaling pathways in different disease contexts. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be used to study its function.

Selective ablation of Tff1-expressing regulatory T cells (Tff1-Tregs) in the lung using an intersectional genetic method promoted pro-inflammatory features of macrophages and exacerbated bleomycin-induced pulmonary fibrosis, indicating the importance of Tff1-Tregs in ameliorating fibrosis [1]. In pancreatic ductal adenocarcinoma, genetic ablation of Tff1 in cells enhanced their sensitivity to gemcitabine treatment, suggesting Tff1 contributes to gemcitabine resistance [3]. Also, IFNγ-dependent silencing of Tff1 during Helicobacter pylori infection was investigated, with IFNγ stimulating C/EBPβ expression which negatively regulates Tff1 [5].

In conclusion, Tff1 plays essential roles in maintaining mucosal integrity and is involved in various disease-related processes. Studies using KO/CKO mouse models have revealed its significance in pulmonary fibrosis, pancreatic cancer drug resistance, and the response to Helicobacter pylori infection, providing insights into potential therapeutic targets for these diseases.