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

J Cell Physiol. 2018 Mar;233(3):2590-2601. doi: 10.1002/jcp.26134. Epub 2017 Sep 4.


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.

Keywords: alopecia areata; fibroblasts; lymphocytes; mouse; programmed cell death ligand.

MeSH terms

  • Alopecia Areata / immunology
  • Alopecia Areata / metabolism*
  • Alopecia Areata / pathology
  • Animals
  • B7-H1 Antigen / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / transplantation
  • Cells, Cultured
  • Coculture Techniques
  • Disease Models, Animal
  • Female
  • Fibroblasts / immunology
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Lymphocyte Activation
  • Mice, Inbred C3H
  • Paracrine Communication
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism*
  • Skin / immunology
  • Skin / metabolism*
  • Skin / pathology
  • Up-Regulation


  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Pdcd1lg2 protein, mouse
  • Programmed Cell Death 1 Ligand 2 Protein