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Increased expression of PD‐L1 and PD‐L2 in dermal fibroblasts from alopecia areata mice

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Journal of Cellular Physiology

Published online on

Abstract

Alopecia areata (AA) is a common autoimmune disorder affecting millions of people worldwide, which manifests as a sudden, non‐scarring hair loss. The expression of a pro‐inflammatory cytokine, interferon‐gamma (INF‐γ), has been well established to be involved in the development of AA. As IFN‐γ and other cytokines are also known to up‐regulate programmed cell death ligand 1 and 2 (PD‐L1 and PD‐L2), which both negatively control immune responses, we asked whether or not a high number of infiltrated T cells, seen in AA lesions, can modulate the expression of PD‐L1 and PD‐L2 in skin cells. From a series of experiments, we showed that a significantly higher number of PD‐L1 or PD‐L2 positive cells affect the skin in AA mice, compared to the skin of non‐AA mice. The number of PD‐L1 positive cells was well correlated with the number of infiltrated T cells, especially CD8+ T cells. We also found that the expression of PD‐L1 and PD‐L2 was co‐localized with type 1 pro‐collagen, CD90 and vimentin, which are biomarkers for dermal fibroblasts. Further studies revealed that releasable factors from activated, but not inactivated, lymphocytes significantly increase the expressions of both PD‐L1 and PD‐L2 in cultured dermal fibroblasts. In conclusion, our findings suggest that the expression of PD‐L1 and PD‐L2 in dermal fibroblasts is up‐regulated by activated T cells in AA‐affected skin, and as such, these regulatory molecules may not exert a negative control of the immune activation seen in AA lesions. (i) The highly expression of PD‐L1 and PD‐L2 were found in AA‐affected skin in a mouse mode; (ii) we identified dermal fibroblasts as the skin cells to express PD‐L1 and PD‐L2 in AA‐affected skin and; (iii) the expressibon of PD‐L1 and PD‐L2 in dermal fibrolasts were regulated by the releasable factors from activated lymphocytes.