Intestinal CD4+ T cells are essential mediators of immune homeostasis and inflammation. system by a single layer of epithelial cells. A specialized population of antigen-presenting cells within the intestine contributes to the generation of IL-10-producing regulatory T cells but also effector T cells expressing IL-17A or IFN-. Naive CD4+ T cells are abundant at inductive sites, but a small proportion of lamina propria CD4+ T cell also display surface markers associated with naive T cells. Trafficking of activated CD4+ T cells to the intestine is regulated Kaempferol-3-O-glucorhamnoside by intestine-specific homing molecules. IL-10, interleukin-10; IFN-, interferon-; HEV, High endothelial Rabbit polyclonal to LACE1 venule. In contrast, intestinal effector sites are characterized by the diffuse distribution of lymphocytes among non-immune cells and matrix, and include the intraepithelial (IEL) compartment and the (LP). The composition of these effector sites demonstrates significant bias toward specific subsets of lymphocytes. Within the IEL compartment, the majority of T cells express CD8, either as the conventional CD8 heterodimer or as a CD8 homodimer 8. Furthermore, the majority of such cells, at least within the small intestine, use a T-cell receptor (TCR) rather than the conventional TCR. While CD4+ T cells, the majority Kaempferol-3-O-glucorhamnoside of which express an TCR, are present within the IEL throughout the intestine, they comprise a greater proportion of T Kaempferol-3-O-glucorhamnoside cells within more distal segments, including the colon 8, 9. Interestingly, IEL CD4+ T-cell populations show significant interstrain variation in mice that may reflect genetic or environmental control 9. Notably, infiltration of the IEL by CD4+ T cells is a feature of inflammation in experimental models of IBD. Within the LP of both the small and large intestines, the majority of T cells are CD4+, with a smaller population of CD8+ cells, although notably the human LP contains a greater proportion of CD8+ T cells compared with the murine gut 10, 11. Similar to their distribution within the IEL, CD4+ T cells may be more highly represented within the colonic LP. In addition to these conventional T-cell subsets, small populations of various unconventional cells, such as CD4?CD8? T cells [including natural killer T (NKT) and mucosal-associated invariant T (MAIT) cells] are present in the healthy LP. The potential role of such cells in intestinal immunity and inflammation has been reviewed elsewhere 12, 13. Within the steady-state LP of both the small intestine and colon, the majority of CD4+ T cells express a CD44hiCD62L? effector memory phenotype of antigen-experienced cells 14, 15. Notable differences exist in the prevailing effector T-cell populations between anatomical niches within the intestine. Acquisition of distinct T-cell effector functions in intestinal niches is discussed in detail below. A small proportion of LP CD4+ T cells (up to 10% within the colonic LP) Kaempferol-3-O-glucorhamnoside display surface markers associated with naive T cells 16. Whether these cells are tissue-resident or are undergoing normal trafficking through the LP is not fully defined, nor is whether they are able to undergo initial priming and differentiation within the LP. Indeed, the contribution of naive T cells in the LP to immunity in the intestine is an area worthy of further study. Intestinal T-cell homing Myeloid antigen-presenting cells (APCs) of the intestine are a heterogeneous population consisting of dendritic cells (DCs) and macrophages. These populations are strategically positioned with the LP and in organized lymphoid structures and exhibit a number of adaptations associated with their dual role in tolerance and immunity in the intestine 17. DCs can act as a bridge with the adaptive immune system through their ability to acquire antigen in the intestine and migrate to the MLN where they prime the activation of naive CD4+ T cells 18. In addition to presenting antigen, intestine-derived DCs are specialized in their ability to prime T-cell responses that are focused on the intestine through the upregulation.