Tolerogenic and immunogenic states of Langerhans cells are orchestrated by epidermal signals acting on a core maturation gene module

Langerhans cells (LCs), residing in the epidermis, are able to induce potent immunogenic responses and also mediate immune tolerance. We propose that tolerogenic of LCs directed by signaling from epidermis involve counter-acting gene circuits coupled a core maturation module. base our analysis on recent genetic genomic findings facilitating understanding molecular mechanisms controlling these divergent functions. Comparing regulatory network (GRN) analyses various types dendritic (DCs) including we integrate signaling-dependent (TGFβ, EpCAM, β-Catenin) transcription factor (IRF4, IRF1, NFκB) regulated appear orchestrate distinctive LC functional states. Our model proposes, while epidermal steady-state promotes function, disruption cell-cell contacts with inflammatory induces programing. The conceptual framework emphasizes sensing discrete cues resident dictating their programing cell state dynamics.