Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
Int J Mol Sci. 2021 May 6;22(9):4909. doi: 10.3390/ijms22094909.
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 -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.
三叶因子家族肽（TFF1、TFF2、TFF3）与粘蛋白一起，是外分泌粘液上皮的典型产物。在这里，它们作为胃肿瘤抑制因子（TFF1）发挥作用，或者在粘膜先天免疫防御中发挥不同的作用（TFF2、TFF3）。微量也作为内分泌物分泌，例如由免疫系统和中枢神经系统分泌。作为一个标志，TFF 肽具有不同的凝集素活性，这在 TFF2 中得到了很好的描述，但也在 TFF1 中得到了描述。在病理上，异位表达发生在炎症和各种肿瘤中。在这篇综述中，讨论了 TFF 肽在炎症中的作用，分为两个层面。一方面，TFF1-3 的表达受炎症信号以不同的方式调节（上游联系）。另一方面，TFF 肽影响炎症过程（下游联系）。在各种缺陷小鼠中，后者得到了最好的认识，这些小鼠具有完全不同的表型。特别是，TFF2 由髓样细胞（如巨噬细胞）和淋巴细胞（如记忆 T 细胞）分泌，在这些细胞中，它调节触发炎症的免疫反应。作为一个新概念，除了凝集素触发的激活外，还讨论了 TFF 肽对糖基化跨膜受体的假设凝集素触发抑制。因此，TFF 是糖免疫学领域的有前途的参与者，如半乳糖凝集素和 C 型凝集素。
