Hair Follicle Mesenchyme-Associated PD-L1 Regulates T-Cell Activation Induced Apoptosis: A Potential Mechanism of Immune Privilege
| Autor: | Jerry Shapiro, Lieping Chen, Eddy Hsi Chun Wang, Kevin J. McElwee, Alice Mui, Nicole Kwong, Trisia Breitkopf, Alexandra K. Marr, Noushin Akhoundsadegh, Garth L. Warnock, Gigi Leung, Jianqiang Hao, Xiaojie Wang, Nicholas Carr |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
T cell
Mesenchyme T-Lymphocytes Gene Expression Apoptosis Dermatology Biology Lymphocyte Activation Peripheral blood mononuclear cell Biochemistry B7-H1 Antigen Mesoderm 03 medical and health sciences 0302 clinical medicine Immune privilege Annexin medicine Immune Tolerance Humans Molecular Biology Cells Cultured 030304 developmental biology 0303 health sciences integumentary system Transfection Dermis Cell Biology Hair follicle Coculture Techniques Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis Hair Follicle Signal Transduction |
| Zdroj: | Journal of Investigative Dermatology. 134(3):736-745 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2013.368 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|