title: Hair follicle mesenchyme-associated PD-L1 regulates T-cell activation induced apoptosis: a potential mechanism of immune privilege.
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.
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Alexandra K
authors.initials: AK
authors.lastname: Marr
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Trisia
authors.initials: T
authors.lastname: Breitkopf
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Gigi
authors.initials: G
authors.lastname: Leung
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Eddy
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kwong
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Noushin
authors.initials: N
authors.lastname: Akhoundsadegh
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Alice
authors.initials: A
authors.lastname: Mui
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Carr
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: Garth.Warnock@vch.ca.
authors.forename: Garth L
authors.initials: GL
authors.lastname: Warnock
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jerry
authors.initials: J
authors.lastname: Shapiro
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: kmcelwee@mail.ubc.ca.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: McElwee
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D060890:B7-H1 Antigen / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D020405:Dermis / Q000166:cytology / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D018859:Hair Follicle / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008648:Mesoderm / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human