Yosuke Ishitsuka*
The epidermal tissue undergoes extensive cross-linkages of the cytoskeleton, ultimately leading to the heavily disulfide cross-linked dead cell layer, the stratum corneum. Therefore, cornification is compared to the anabolic metabolism of sulfur. The leaky para cellular barrier enables antigen-presenting cells to access foreign substances easily and enhanced antigen uptake at the Tight Junction (TJ) is considered the atopic march’s culprit. However, the sound epidermal structure cannot be obtained without the thiol-rich cytoskeletal protein loricrin. The down regulation of loricrin not only represents atopic dermatitis pathology but also affects the epidermal metabolism. The metabolic microenvironment genetically reprograms the monocyte-macrophage systems that can tailor-made local adaptive immune responses. Therefore, we reasoned that cornifying keratinocytes, which undergo myriad metabolic pathways above the TJ, could control the distal immune effector functions by directly affecting the gene expression program of cutaneous immune effector function.