Hair follicle mesenchyme-associated PD-L1 regulates T-cell activation induced apoptosis: A potential mechanism of immune privilege

Xiaojie Wang, Alexandra K. Marr, Trisia Breitkopf, Gigi Leung, Jianqiang Hao, Eddy Wang, Nicole Kwong, Noushin Akhoundsadegh, Lieping Chen, Alice Mui, Nicholas Carr, Garth L. Warnock, Jerry Shapiro, Kevin J. McElwee

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23 Citations (Scopus)

Abstract

The immune privilege (IP) of hair follicles (HFs) has been well established in previous studies. However, whether cultured HF cells still exhibit IP properties, the individual factors involved in this process, and the detailed mechanisms that drive and maintain IP, are largely unidentified. We found preferential expression of IP-associated genes in cultured HF dermal papilla and dermal sheath cup cells (DSCCs) compared with non-follicular fibroblasts (FBs) at passage 4, suggesting a potential for functional IP. Notably, programmed cell death 1 ligand 1 (PD-L1) was significantly upregulated in DSCCs and dermal papilla cells relative to FBs. IFNγ secretion from peripheral blood mononuclear cells (PBMCs) co-cultured with histoincompatible DSCCs was significantly lower than with FB and higher percentages of early apoptotic, Annexin V + cells were observed in PBMC co-cultured with DSCCs. Knockdown of PD-L1 translation by silencing interfering RNA in DSCCs enabled increased IFNγ secretion by PBMCs, whereas transfection of pCMV6-XL4/hPD-L1 in FB significantly reduced IFNγ secretion and increased apoptosis in co-cultured PBMCs. We also found that apoptosis in allogeneic T cells induced by DSCCs was largely dependent on the mitochondrial pathway. Our study suggests IP properties are exhibited in cultured DSCCs in part through expression of negative co-signaling molecule PD-L1.

Original languageEnglish
Pages (from-to)736-745
Number of pages10
JournalJournal of Investigative Dermatology
Volume134
Issue number3
DOIs
Publication statusPublished - Mar 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Wang, X., Marr, A. K., Breitkopf, T., Leung, G., Hao, J., Wang, E., Kwong, N., Akhoundsadegh, N., Chen, L., Mui, A., Carr, N., Warnock, G. L., Shapiro, J., & McElwee, K. J. (2014). Hair follicle mesenchyme-associated PD-L1 regulates T-cell activation induced apoptosis: A potential mechanism of immune privilege. Journal of Investigative Dermatology, 134(3), 736-745. https://doi.org/10.1038/jid.2013.368