Regulation and function of E-cadherin. (A) LCs. (B) DCs. (C) Macrophages. (A) TGF-β induces E-cadherin in LCs, which is crucial for the maintenance of an immature LC pool in the epidermis.⁶⁹  Retention in the skin is mediated by E-cadherin-dependent adhesion to keratinocytes. In addition, E-cadherin ligation on LCs prevents the maturation of these cells.⁷²  Inflammatory stimuli decrease E-cadherin expression on LCs, resulting in their migration to the LNs and maturation.^70,71  (B) On disruption of E-cadherin–mediated clusters or on GSK-3β inhibition, DCs undergo a partial maturation program toward tolerogenic DCs under the influence of β-catenin activity.³⁶  This β-catenin–mediated induction of tolerogenic DC is inhibited by TGF-β.⁷⁵  (C) E-cadherin is a selective marker for IL-4/IL-13–exposed macrophages and is STAT6/DAP12/polyamine-dependently induced.^90,94,99  TGF-β synergizes with IL-4/IL-13 for maximal Cdh1 gene induction, whereas IFNγ and lipopolysaccharide inhibit E-cadherin expression.⁹⁰  E-cadherin forms a functional complex with its catenins, allowing them to engage in homotypic interactions (IL-4–driven macrophage fusion and osteoclastogenesis)^90,99  and heterotypic interactions (with CD103⁺ and KLRG1⁺ T cells).⁹⁰