Figure 2.

Modulation of immune responses by EVs originated from intestinal epithelial and immune cells. Schematic view of the intestinal mucosa showing the epithelium and the underlying immune system. These host cells receive information from microbiota mainly through secreted factors and lumen antigens that can diffuse through the mucus layer and initiate appropriate immune responses. In this scenario, EVs are key for the host to communicate with neighboring cells. Intestinal epithelial cells (IECs) release EVs from the basolateral side (colored in brown) that participate in the crosstalk with lymphocytes and dendritic cells, being able to activate naïve T cells towards immunogenic (Th) or tolerogenic (Treg) responses depending on the exosome-expressed epitopes and cargo. DCs are the main antigen-presenting cells in the gut lamina propria. These immune cells can integrate information either directly from the intestinal lumen or transmitted through EVs secreted by other cell types under healthy and pathological conditions (intestinal infections, inflammation, or cancer). Once activated, DCs secrete EVs (colored in purple) containing MHC and costimulatory molecules that mediate antigen presentation and immunomodulatory effects towards CD4+ or CD8+ T cells, eliciting suitable T cell responses.