Keratinocytes Regulate the Threshold of Inflammation by Inhibiting T Cell Effector Functions

• Published in: Cells
• Main Authors: Peter Seiringer, Stefanie Eyerich, Kilian Eyerich, Daniela Dittlein, Anna Caroline Pilz, Emanuele Scala, Johannes Ring, Heidrun Behrendt, Andrea Cavani, Claudia Traidl-Hoffmann
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Subjects: keratinocytes; T cells; T cell effector functions; skin immune homeostasis; skin barrier
• Online Access: https://www.mdpi.com/2073-4409/10/7/1606

Whilst the importance of keratinocytes as a first-line defense has been widely investigated, little is known about their interactions with non-resident immune cells. In this study, the impact of human keratinocytes on T cell effector functions was analyzed in an antigen-specific in vitro model of allergic contact dermatitis (ACD) to nickel sulfate. Keratinocytes partially inhibited T cell proliferation and cytokine production. This effect was dependent on the keratinocyte/T cell ratio and was partially reversible by increasing the number of autologous dendritic cells. The inhibition of T cell proliferation by keratinocytes was independent of the T cell subtype and antigen presentation by different professional antigen-presenting cells. Autologous and heterologous keratinocytes showed comparable effects, while the fixation of keratinocytes with paraformaldehyde abrogated the immunosuppressive effect. The separation of keratinocytes and T cells by a transwell chamber, as well as a cell-free keratinocyte supernatant, inhibited T cell effector functions to the same amount as directly co-cultured keratinocytes, thus proving that soluble factor/s account for the observed suppressive effects. In conclusion, keratinocytes critically control the threshold of inflammatory processes in the skin by inhibiting T cell proliferation and cytokine production.