Figure 2: Polarization of different Th cell subpopulations by one inflammatory signal and three DC derived signals. Skin resident LCs and dermal DCs recognize a complex of skin penetrating haptens and proteins via PRRs. Subsequently, these cells mature and display antigenic epitopes to TCR bearing T cells in the lymph node. The allergen is presented by MHC molecules (signal 1) and costimulatory molecules deliver a signal 2. The profile of differentiating cytokines and growth factors released by activated DCs is crucial for the development of individual Th cells. These are characterized by expression of transcription factors such as T-bet, GATA3, RORC (human counterpart of murine RORγt), FOXO4, and release of signature cytokines such as IFN-γ for Th1, IL-4 for Th2, IL-17 for Th17, and IL-22 for Th22. PRR, pattern recognition receptor; Th, T helper cell.