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Increased expression of PD‐L1 and PD‐L2 in dermal fibroblasts from alopecia areata mice
Author(s) -
Li Yunyuan,
Kilani Ruhi T.,
Pakyari Mohammadreza,
Leung Gigi,
Nabai Layla,
Ghahary Aziz
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26134
Subject(s) - alopecia areata , immune system , cd8 , pd l1 , cytokine , chemistry , immunology , fibroblast , medicine , biology , immunotherapy , in vitro , biochemistry
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.