Gut-specific homing

Gut-specific homing is the mechanism by which activated T cells and antibody-secreting cells (ASCs) are targeted to both inflamed and non-inflamed regions of the gut in order to provide an effective immune response. This process relies on the key interaction between the integrin α4β7 and the addressin MadCAM-1 on the surfaces of the appropriate cells. Additionally, this interaction is strengthened by the presence of CCR9, a chemokine receptor, which interacts with TECK. Vitamin A-derived retinoic acid regulates the expression of these cell surface proteins. Gut-specific homing is the mechanism by which activated T cells and antibody-secreting cells (ASCs) are targeted to both inflamed and non-inflamed regions of the gut in order to provide an effective immune response. This process relies on the key interaction between the integrin α4β7 and the addressin MadCAM-1 on the surfaces of the appropriate cells. Additionally, this interaction is strengthened by the presence of CCR9, a chemokine receptor, which interacts with TECK. Vitamin A-derived retinoic acid regulates the expression of these cell surface proteins. T cells are produced in the thymus, and upon leaving they migrate to and around the lymphoid organs of the body, including lymph nodes. In the paracortex of the lymphoid nodes they are exposed to professional antigen-presenting cells (APCs), such as dendritic cells (DCs). Specific interactions between the naïve T cells and their cognate antigens result in T cell activation. The activated T cells, immunoblasts, undergo clonal expansion before acquiring effector functions. The activated T cells then emigrate from the lymph nodes, via the efferent lymphatic vessel, and migrate around the body in the blood. In certain circumstances, some activated T cells show a preference for patrolling certain tissues. This has been termed lymphocyte homing. Gut-specific homing is the preferential movement of activated T cells to the intestine and the gut. In this way T cells are effectively recruited to form part of the first line of defense against pathogens. This is because T cells are targeted to and recirculated around primary infection sites. Overall this results in an extremely high concentration of lymphocytes in this region; 70% of the immunoglobulin-producing cells are found in the mucosal surfaces of the body. It was first suggested by Griselli that there were different pathways of T cell migration. Initial theories that the T cells were targeted not to the tissue but to the antigens were disproved, as work by Cahill showed that purified T cells would relocate to the region of activation. For example, T cells activated in the Peyer's patch lymph nodes, found in the gut, would return to the gut. Subsequent work looked to explain the cause of this T cell targeting. Originally it was theorized that the micro-environment of lymphoid tissues provided the cues for the preferential homing of lymphocytes. While this may be the case to some extent, it is now widely held that the main driver in lymphocyte homing is the interactions between T cell adhesion molecules (lymphocyte homing receptors) and ligands (addressins) on the tissue high endothelial venules (HEVs). This theory arose from the observation that the cell surface integrins varied between different T cell populations. Work began to identify the differences and what they meant for T cell migration. It became apparent that there were significantly higher levels of the integrin α4β7 on activated T cells in comparison to naïve T cells. Additionally, this integrin was much more common on CD8+ T cells activated in the Peyer's patches (PP T-cells) compared to other T cell subsets, such as peripheral and mesenteric lymph nodes activated T cells.