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

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.

Stress signalling and STAT1 activation characterize the keratinocytic gene expression pattern in Hidradenitis suppurativa

“…Hence, their regulation in epidermal HS lesions may reflect a conserved epidermal responsiveness to high levels of those cytokines, which contribute to T‐cell dysregulation and may initiate and sustain chronic inflammation in HS 7 . On the other hand, the response pattern might also mirror the control of inflammatory processes in the dermis by lesional HS keratinocytes, which may inhibit T‐cell proliferation and cytokine production as recently suggested for allergic contact dermatitis 38 (Fig. S3).…”

Mechanistic insights into the interactions between cancer drivers and the tumour immune microenvironment

“…4D ). Keratinocytes have recently been reported to inhibit T cell proliferation by secreting T cell-modulating cytokines 35 . This could explain how DNMT3B amplification could lead to higher immune infiltration.…”

Anti-inflammatory potential of platinum nanozymes: mechanisms and perspectives

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