ArticleJournal of autoimmunity2014
Programmed cell death 1 (PD-1) regulates the effector function of CD8 T cells via PD-L1 expressed on target keratinocytes.
Article in Journal of autoimmunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 65 citations in OpenAlex.
- Rapid progression to toxic epidermal necrolysis following switch of PD-1 inhibitors: a case report.Frontiers in medicine · 2026Article
- Immunomodulation of UVB-induced regulatory T cells prevents the establishment of squamous cell carcinoma.Journal for immunotherapy of cancer · 2025Article
- CD8 T cells mediate immunosurveillance for neoantigen+ epithelial stem cells in the colon.bioRxiv : the preprint server for biology · 2025Article
- Clinical features, treatment, and prognosis of pembrolizumab -induced Stevens-Johnson syndrome / toxic epidermal necrolysis.Investigational new drugs · 2025Article
- Two cases of severe oral mucositis caused by atezolizumab plus bevacizumab combination therapy for hepatocellular carcinoma.Clinical journal of gastroenterology · 2024Article
- Galectin 7 leads to a relative reduction in CD4+ T cells, mediated by PD-1.Scientific reports · 2024Article
- Inhibition of UV-Induced Stress Signaling and Inflammatory Responses in SKH-1 Mouse Skin by Topical Small-Molecule PD-L1 Blockade.JID innovations : skin science from molecules to population health · 2024Article
- Immune-related toxic epidermal necrolysis affecting trachea mucosal epithelium: a case report and literature review.Frontiers in pharmacology · 2024Article
- Frequency of peripheral PD-1British journal of cancer · 2023Article
- Advances in cutaneous squamous cell carcinoma.Nature reviews. Cancer · 2023Review
- Review: PD-L1 as an emerging target in the treatment and prevention of keratinocytic skin cancer.Molecular carcinogenesis · 2023Review
- Immune cell subsets in interface cutaneous immune-related adverse events associated with anti-PD-1 therapy resemble acute graft versus host disease more than lichen planus.Journal of cutaneous pathology · 2022Article
- Immunohistochemical Study of the PD-1/PD-L1 Pathway in Cutaneous Lupus Erythematosus.Pathology oncology research : POR · 2022Article
- Skin Manifestation Induced by Immune Checkpoint Inhibitors.Clinical, cosmetic and investigational dermatology · 2022Review
- Clinicoprognostic and Histopathological Features of Guttate and Plaque Psoriasis Based on PD-1 Expression.Journal of clinical medicine · 2021Article
- Cyclic AMP Response Element Modulator-α Suppresses PD-1 Expression and Promotes Effector CD4Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- The role of the programmed cell death protein-1/programmed death-ligand 1 pathway, regulatory T cells and T helper 17 cells in tumor immunity: a narrative review.Annals of translational medicine · 2020Review
- Activation of CD8 T cells accelerates anti-PD-1 antibody-induced psoriasis-like dermatitis through IL-6.Communications biology · 2020Article
- Inactivation of the PD-1-Dependent Immunoregulation in Mice Exacerbates Contact Hypersensitivity Resembling Immune-Related Adverse Events.Frontiers in immunology · 2020Article
- Elucidating the Efficacy of the Bacille Calmette-Guérin Vaccination in Conjunction with First Line Antibiotics and Liposomal Glutathione.Journal of clinical medicine · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Programmed cell death 1 (PD-1) is an inhibitory molecule expressed by activated T cells. Its ligands (PD-L1 and -L2; PD-Ls) are expressed not only by a variety of leukocytes but also by stromal cells. To assess the role of PD-1 in CD8 T cell-mediated diseases, we used PD-1-knockout (KO) OVA-specific T cell-receptor transgenic (Tg) CD8 T cells (OT-I cells) in a murine model of mucocutaneous graft-versus-host disease (GVHD). We found that mice expressing OVA on epidermal keratinocytes (K14-mOVA mice) developed markedly enhanced GVHD-like disease after transfer of PD-1-KO OT-I cells as compared to those mice transferred with wild-type OT-I cells. In addition, K14-mOVA × OT-I double Tg (DTg) mice do not develop GVHD-like disease after adoptive transfer of OT-I cells, while transfer of PD-1-KO OT-I cells caused GVHD-like disease in a Fas/Fas-L independent manner. These results suggest that PD-1/PD-Ls-interactions have stronger inhibitory effects on pathogenic CD8 T cells than does Fas/Fas-L-interactions. Keratinocytes from K14-mOVA mice with GVHD-like skin lesions express PD-L1, while those from mice without the disease do not. These findings reflect the fact that primary keratinocytes express PD-L1 when stimulated by interferon-γ in vitro. When co-cultured with K14-mOVA keratinocytes for 2 days, PD-1-KO OT-I cells exhibited enhanced proliferation and activation compared to wild-type OT-I cells. In addition, knockdown of 50% PD-L1 expression on the keratinocytes with transfection of PD-L1-siRNA enhanced OT-I cell proliferation. In aggregate, our data strongly suggest that PD-L1, expressed on activated target keratinocytes presenting autoantigens, regulates autoaggressive CD8 T cells, and inhibits the development of mucocutaneous autoimmune diseases.
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Registered trials
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