Variations in co-signal ligand expression and cytokine production greatly influence the antigen-presenting properties of migrating DCs in regional lymph nodes (RLNs). Here we investigated DCs migrating from the oral mucosa using CD326 and CD103 antigens for discriminate CD207(+) Langerhans cells (LCs) from CD207(+). submucosal DCs (SMDCs). Similar to DCs migrating from the skin, we identified four distinct oral mucosal DC (OMDC) subsets, CD11c(hi)CD207(-)CD103(-)CD326(int)CD11b(hi) (F1; resident CD11b(hi) SMDCs), CD11c(int)/(lo)CD207(-)CD103(-)CD326(lo)CD11b(int/hi) (F2; newly recruited blood-derived SMDCs), CD11(int/) 1 (lo)CD207(+)CD103(+)CD326(int/hi)CD11b(lo) (CD103(+). F3; resident CD207(+) SMDCs), and CD11c(int/) (lo)CD207(+)CD103(-)CD326(int)/(hi)CD11b(lo) (CD103(-) F3; resident LCs). F1 DCs migrated rapidly after fluorescein isothiocyanate (FITC) painting and expressed notably high levels of CD86, CD273, and CD274 at an earlier time point. In contrast, CD103(-) LCs expressing the highest levels of the epithelial cell adhesion molecule CD326 accounted for a minor subset at the earlier time point, but increased slowly with CD103(+)CD207(+) SMDCs. However, their expression of CD86. CD273, and CD274 was very limited. The delayed migration and limited induction of co-signal ligands suggest that roles of OMLCs are distinct from those of the other three DC subsets. The identification of distinct subsets of OMDCs in RLNs may benefit efforts to determine the functional specialization of each subset in T cell responses against orally administrated antigens. (C) 2011 Elsevier Inc. All rights reserved.