Abstract
Trefoil factor family peptides (TFF1, TFF2, TFF3), together with mucins, are typical exocrine products of mucous epithelia. Here, they act as a gastric tumor suppressor (TFF1) or they play different roles in mucosal innate immune defense (TFF2, TFF3). Minute amounts are also secreted as endocrine, e.g., by the immune and central nervous systems. As a hallmark, TFF peptides have different lectin activities, best characterized for TFF2, but also TFF1. Pathologically, ectopic expression occurs during inflammation and in various tumors. In this review, the role of TFF peptides during inflammation is discussed on two levels. On the one hand, the expression of TFF1-3 is regulated by inflammatory signals in different ways (upstream links). On the other hand, TFF peptides influence inflammatory processes (downstream links). The latter are recognized best in various Tff-deficient mice, which have completely different phenotypes. In particular, TFF2 is secreted by myeloid cells (e.g., macrophages) and lymphocytes (e.g., memory T cells), where it modulates immune reactions triggering inflammation. As a new concept, in addition to lectin-triggered activation, a hypothetical lectin-triggered inhibition of glycosylated transmembrane receptors by TFF peptides is discussed. Thus, TFFs are promising players in the field of glycoimmunology, such as galectins and C-type lectins.
Highlights
In spite of their overall similarity, there is probably a major structural difference between TFF1 and TFF3 concerning the nucleophilicity of CysVII, which is enhanced in TFF1 by steric exposure
The protective effect of TFF2 from dextran sulfate sodium (DSS)-induced colitis seemed to originate from colonic epithelial cells and not from colonic leucocytes, as TFF2 is not synthesized in the latter [17]. In another animal model of intestinal inflammation, Tff2KO mice were orally infected with T. gondii [153]
[8,23,36,45], an interSuch a lectin interaction could alsoofhave the advantage being specific for a cell type, action of TFF2 with the carbohydrate moietystatus of CXCR4 would be not surprising
Summary
Secretory trefoil factor family (TFF) peptides comprise TFF1, TFF2, and TFF3 (reviews: [1,2,3,4]). TFF2 contains two TFF domains and two additional cysteine residues, the latter connecting the C- and N-terminal via a disulfide bridge (Figure 1). TFF2 contains an additional disulfide bridge between Cys-6 and Cys-104 creating a fide bridge between Cys-6 and Cys-104 creating a circular structure; represented are the procircular structure; represented are the proline residues (P) at the C-terminal outside the TFF domains. The major amounts of TFF peptides are secreted from mucous epithelia, where they are. The major amounts of TFF peptides are secreted from mucous epithelia, where they released together with mucins in an exocrine manner [4,11,12,13]. Minute amounts of TFF peptides undergo endocrine examples are lymphoid organs and tissues The effects observed were not really convincing as−they were hardly de-above [4,12,20]
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