Keratinocytes Regulate the Threshold of Inflammation by Inhibiting T Cell Effector Functions.
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| Abstract |
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.
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| Authors | Peter Seiringer, Stefanie Eyerich, Kilian Eyerich, Daniela Dittlein, Anna Caroline Pilz, Emanuele Scala, Johannes Ring, Heidrun Behrendt, Andrea Cavani, Claudia Traidl-Hoffmann |
| Journal | Cells (Cells) Vol. 10 Issue 7 (06 26 2021) ISSN: 2073-4409 [Electronic] Switzerland |
| PMID | 34206914 (Publication Type: Journal Article) |
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