Previous studies have demonstrated that the numbers of interfollicular epidermal stem cells (IFE‐SCs) and dermal stem cells (DSCs) decrease with age and that this decrease is attributed to the age‐related deterioration of skin homeostatic functions and the delay in wound healing. Meanwhile, functional decline in the stem cells is also considered to be responsible for the deteriorated skin homeostatic functions and the delayed wound healing associated with ageing. In the present study, we focused on epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) signalling and fibroblast growth factor‐2/fibroblast growth factor receptor (FGF2/FGFR) signalling to analyse the age‐related changes. Immunohistological analysis revealed that the expressions of EGFR and FGFR1 declined in IFE‐SCs and DSCs with age, respectively. Additionally, IFE‐SCs and DSCs isolated from the skin samples of elderly subjects exhibited lowered responsiveness to EGF and FGF2, respectively. These results suggest that the lowered responsiveness of the skin stem cells to growth factors may be a factor involved in the age‐related deterioration of skin regenerative functions during wound healing and skin homeostatic functions. We hope that homeostatic and wound healing functions in the skin could be maintained if the decreased expressions of EGFR and FGFR1 in IFE‐SCs and DSCs, respectively, can be suppressed.

L-type amino acid transporter 1 (LAT1), a transporter of large neutral amino acids, is rarely expressed in resting T cells, whereas its expression is remarkably upregulated upon activation. We have proven the essential role of T cells in the development of allergic inflammation in various target organs, though the contribution of LAT1 to T cell function in allergic diseases has not been clarified. Here, we investigated the effect of a LAT1 inhibitor, JPH203, on antigen-induced inflammatory responses in the skin, lungs, and nasal mucosa of immunized mice or mice transferred with in vitro-differentiated antigen-specific Th2 cells. Consistent with the augmented expression of LAT1 in skin-accumulated CD4+ T cells of atopic dermatitis patients, antigen-induced skin inflammation with eosinophil infiltration and Th2 cytokine production developed in immunized and Th2 cell-transferred mice was suppressed by JPH203 treatment. Essentially the same efficacy of JPH203 was seen in antigen-induced nasal eosinophilic inflammation accompanied by nasal hyperresponsiveness evoked in both mice. Remarkably, antigen-induced bronchial hyperresponsiveness was suppressed, whereas lung accumulation of eosinophils or antigen-specific T cells was not affected, by JPH203 in Th2 cell-transferred mice. The blockade of LAT1-mediated glycolysis, oxidative phosphorylation, and activating transcription factor 4-regulated amino acid starving responses in cytokine production and proliferation of Th2 was suggested to be involved in the efficacy of JPH203. LAT1 is essential for the pathogenesis of activated Th2 cell-mediated allergic inflammation and would be a promising target for the development of new means to treat allergic diseases.

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