ArticleCellular & molecular immunology2020
Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin.
Article in Cellular & molecular immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 51 citations in OpenAlex.
- Single-cell transcriptome revealed the aberrant keratinocytes activation in antigen presentation in atopic dermatitis.Annals of medicine · 2026Article
- Downregulation of SPRED1 drives keratinocyte hyperproliferation in psoriasis via activation of the ERK-RSK1 signaling axis.iScience · 2026Article
- Epidermal MHC-II-mediated NK cell recruitment triggers keratinocyte pyroptosis, facilitating pathogenesis of psoriasis.Experimental & molecular medicine · 2026Article
- Skin barrier dysfunction and correlation with the onset and progression of psoriasis.Frontiers in immunology · 2026Review
- CD2 costimulation strength: A key regulator of T cell function and anti-tumor immunity that is epigenetically regulated.iScience · 2025Article
- S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis.Immunity · 2025Article
- Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics.JID innovations : skin science from molecules to population health · 2025Article
- TYK2 rs34536443 (P1104A) Variant Suppresses ICAM1-Mediated Inflammation: Insights From Mendelian Randomization and Functional Analyses.Psoriasis (Auckland, N.Z.) · 2025Article
- Antigen-presenting fibroblasts: emerging players in immune modulation and therapeutic targets.Theranostics · 2025Review
- A potential prognostic marker for hematologic neoplasms: CD58.Frontiers in oncology · 2025Review
- Keratinocyte-Mediated Antigen Presentation in Psoriasis: Preliminary Insights from In Vitro Studies.International journal of molecular sciences · 2024Article
- CD2 expressing innate lymphoid and T cells are critical effectors of immunopathogenesis in hidradenitis suppurativa.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Spatial Mass Cytometry-Based Single-Cell Imaging Reveals a Disrupted Epithelial-Immune Axis in Prurigo Nodularis.The Journal of investigative dermatology · 2024Article
- Revisiting T-cell adhesion molecules as potential targets for cancer immunotherapy: CD226 and CD2.Experimental & molecular medicine · 2024Review
- The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis.Nature communications · 2024Article
- The Immunology of Psoriasis-Current Concepts in Pathogenesis.Clinical reviews in allergy & immunology · 2024Review
- Comparative analysis of whole plant, flower and root extracts ofFrontiers in immunology · 2024Article
- Identification of driving genes of familial adenomatous polyposis by differential gene expression analysis and weighted gene co-expression network analysis.Technology and health care : official journal of the European Society for Engineering and Medicine · 2024Article
- Article
- Dose-Response Efficacy and Mechanisms of Orally AdministeredNutrients · 2023Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interplay between keratinocytes and immune cells, especially T cells, plays an important role in the pathogenesis of chronic inflammatory skin diseases. During psoriasis, keratinocytes attract T cells by releasing chemokines, while skin-infiltrating self-reactive T cells secrete proinflammatory cytokines, e.g., IFNγ and IL-17A, that cause epidermal hyperplasia. Similarly, in chronic graft-versus-host disease, allogenic IFNγ-producing Th1/Tc1 and IL-17-producing Th17/Tc17 cells are recruited by keratinocyte-derived chemokines and accumulate in the skin. However, whether keratinocytes act as nonprofessional antigen-presenting cells to directly activate naive human T cells in the epidermis remains unknown. Here, we demonstrate that under proinflammatory conditions, primary human keratinocytes indeed activate naive human T cells. This activation required cell contact and costimulatory signaling via CD58/CD2 and CD54/LFA-1. Naive T cells costimulated by keratinocytes selectively differentiated into Th1 and Th17 cells. In particular, keratinocyte-initiated Th1 differentiation was dependent on costimulation through CD58/CD2. The latter molecule initiated STAT1 signaling and IFNγ production in T cells. Costimulation of T cells by keratinocytes resulting in Th1 and Th17 differentiation represents a new explanation for the local enrichment of Th1 and Th17 cells in the skin of patients with a chronic inflammatory skin disease. Consequently, local interference with T cell-keratinocyte interactions may represent a novel strategy for the treatment of Th1 and Th17 cell-driven skin diseases.
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