Keratinocytes costimulate naive human T cells via CD2

• Verfasst von: Orlik, Christian [VerfasserIn]
• Verfasst von: Deibel, Daniel [VerfasserIn]
• Verfasst von: Kramer, Johanna [VerfasserIn]
• Verfasst von: Balta, Emre [VerfasserIn]
• Verfasst von: Ganskih, Sabina [VerfasserIn]
• Verfasst von: Habicht, Jüri [VerfasserIn]
• Verfasst von: Niesler, Beate [VerfasserIn]
• Verfasst von: Schröder-Braunstein, Jutta [VerfasserIn]
• Verfasst von: Schäkel, Knut [VerfasserIn]
• Verfasst von: Wabnitz, Guido H. [VerfasserIn]
• Verfasst von: Samstag, Yvonne [VerfasserIn]
• Titel: Keratinocytes costimulate naive human T cells via CD2
• Titelzusatz: a potential target to prevent the development of proinflammatory Th1 cells in the skin
• Verf.angabe: Christian Orlik, Daniel Deibel, Johanna Küblbeck, Emre Balta, Sabina Ganskih, Jüri Habicht, Beate Niesler, Jutta Schröder-Braunstein, Knut Schäkel, Guido Wabnitz and Yvonne Samstag
• Jahr: 2020
• Jahr des Originals: 2019
• Umfang: 15 S.
• Fussnoten: Published online: 19 July 2019 ; Gesehen am 06.04.2020
• Titel Quelle: Enthalten in: Cellular & molecular immunology
• Ort Quelle: London [u.a.] : Nature Publ. Group, 2004
• Jahr Quelle: 2020
• Band/Heft Quelle: 17(2020), 4, Seite 380-394
• ISSN Quelle: 2042-0226
• DOI: doi:10.1038/s41423-019-0261-x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1694097609

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.