SC barrier damages induce danger signals in the epidermis. After SC barrier abrogation, protease-active allergens and uncontrolled intrinsic proteases, as well as bacterial molecules such as lipoteichoic acid of gram-positive bacteria, might agonize Par2 and TLRs on keratinocytes, respectively (7, 55, 112, 123). Keratinocytes then produce TNF-α, IL-1, and thymic stromal lymphopoietin (TSLP) (47, 55), in response to which LCs become activated (54, 56, 124). Alternatively, protease-active allergens might directly obscure the TJ barrier and then penetrate the epidermis (7), where they directly or indirectly activate LCs. Upon SC perturbation, dendrites of activated LCs penetrate the TJs to take up protease-active or -inactive antigens from the extra-TJ environment (13). Such percutaneous sensitization and chronic allergen challenge via different routes, such as the lungs, nasal cavities, and intestinal tract, are speculated to manifest as the atopic march.