The role of the ionotropic glutamate receptor NMDAR on αβ T cells of the intestinal mucosa in an experimental murine model of colitis

T cells, located mainly in the intestinal mucosa, play an important role in tolerance to microbiota and food antigens. Recently, it was discovered that T cells express receptors for neurotransmitters, including the ionotropic glutamate receptor NMDAR. Glutamate is the main excitatory neurotransmitter and is responsible for intestinal motility and homeostasis. However, little is known about the role of NMDAR on intestinal T cells. Therefore, we decided to investigate this through the specific deletion of NMDAR on T cells using Cd4^CrexGrin1^f/f mice. In an acute DSS-induced colitis model, an increase of CD4+ T cells and a decrease of CD8+ T cells frequencies in the lamina propria of the cecum and colonic intraepithelial compartment were observed in Cd4^CrexGrin1^f/f mice. In addition, these CD4+ T cells from the lamina propria of the cecum produced more IL-17. In a chronic colitis model induced by multiple cycles of DSS, CD4+ T cells from colonic lamina propria were reduced and an increase of IFN-γ production by these cells were found in Cd4^CrexGrin1^f/f mice. Finally, we also evaluated an adoptive transfer colitis model. The transfer of NMDAR-depleted CD4+ T cells to Rag1^-/- mice generated an increase of CD4+ T cells, as well as a reduction of CD103 and IL-17 and IFN-γ production by these cells in the mesenteric and cecal lymph node. Taken together, our data suggest the involvement of NMDAR expressed by αβ T cells in controlling the intestinal homeostasis.