The interaction between the intestinal epithelium and T cells is hindered in many diseases, causing T-cell activation, recruitment, disruption, and depletion. It was hypothesized that the activation of T-cells leads to the regulation of the epithelial barrier function, which works by targeting the tight junction complex assembly. This study aimed to investigate the bidirectional communication between activated T cells and IECs and identify the mechanisms by which T cells regulate paracellular permeability and modulate barrier integrity. In vitro 2-D and a 3-D co-culture model were developed, which were then used to show that activated T lymphocytes initiate a response in the epithelium that increases barrier integrity initially. This enhanced barrier function is either maintained or rapidly reversed, depending on the initial T-cell receptor stimulus duration and whether the synthesis of the resulting cytokines is transient or continuous.

IECs are in continuous communication with subjacent immune cells, ensuring a healthy and immunologically protective physical barrier.  Mechanistic evidence was provided that IEC T-cell communication modulates paracellular epithelial permeability by regulating TJ assembly and cell morphology and alters the epithelium’s homeostatic immune properties. By evaluating the bidirectional communication using non-transformed epithelial cells as organoid cultures, further studies will be more advanced. Overall, the results highlight that in the setting of acute intestinal inflammation, the epithelium initially responds by strengthening its barrier function. Nevertheless, chronic immune exposure disrupts the epithelium and enhances microbial translocation.