Plet1-Mediated Cell Detachment Controls Steady State Migration of Dendritic Cells in the Intestine

Migration of dendritic cells (DC) from mucosal tissues to draining lymph nodes (LN) is a prerequisite for induction of normal and pathogenic T cell responses. DC migration is controlled by the chemokine receptor CCR7, which guides cells through the extracellular matrix (ECM) of the intestinal lamina propria (LP). However, the molecular mechanisms that control DC mobilization and detachment are incompletely understood. We recently identified the GPI-anchored surface protein Placenta-expressed transcript 1 (Plet1) as specifically expressed on CD11c⁺MHCII^hi, CCR7⁺ migratory DC in the gut-draining LN and LP. Plet1⁺ DC subsets analysis revealed that Plet1 expression was highly enriched on CD103⁺CD11b⁺ DC, both at steady state, and during inflammation. Plet1 deficiency did not affect chemokine responses as Plet1^-/- DC showed normal CCR7-mediated migration in vitro.  Structure-prediction analyses of the Plet1 protein, and in vitro adhesion assays suggest a role of Plet1 in modulating ECM-integrin interactions by DC. This was confirmed in vivo, as migration of LP DC was severely impaired in the absence of Plet1: Plet1^-/- DCs failed to migrate to the LN and accumulated within the LP. Taken together, these data unravel a previously unappreciated mechanism where Plet1 controls DC migration via their detachment from the ECM in the intestine.