Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin
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...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
2020
|
| In: |
Cellular & molecular immunology
Year: 2019, Volume: 17, Issue: 4, Pages: 380-394 |
| ISSN: | 2042-0226 |
| DOI: | 10.1038/s41423-019-0261-x |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41423-019-0261-x Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41423-019-0261-x 
|
| Author Notes: | Christian Orlik, Daniel Deibel, Johanna Küblbeck, Emre Balta, Sabina Ganskih, Jüri Habicht, Beate Niesler, Jutta Schröder-Braunstein, Knut Schäkel, Guido Wabnitz and Yvonne Samstag |
| Summary: | 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. |
|---|---|
| Item Description: | Published online: 19 July 2019 Gesehen am 06.04.2020 |
| Physical Description: | Online Resource |
| ISSN: | 2042-0226 |
| DOI: | 10.1038/s41423-019-0261-x |