Fig. 3.
TRM cell differentiation. Naïve T cells can be reversibly preconditioned in homeostasis and imprinted during activation by migratory DCs to become TRM cells through TGF-β signaling. Migratory DCs can also instruct T cells to home into the same non-lymphoid tissue they came from. For instance, intestinal and cutaneous migrating DCs, by metabolizing respectively vitamin A and vitamin D, induce the expression of chemokine receptors guiding activated T cell homing into the gut and the skin. Recently activated effector T cells reach the inflamed non-lymphoid tissues through arterial circulation and extravasate also thanks to the competition between CD69 and S1PR1. Here, a subset of effector TRM precursor cells upregulates the expression of tissue-retention molecules (e.g., CD103, CD49a, and CXCR6) in response to TGF-β and IL-12, differentiating into long-lived TRM cells. Re-encountering the cognate antigen presented by professional and non-professional antigen-presenting cells may enhance the establishment of TRM cells