A skewed pool of resident T cells triggers psoriasis-associated tissue responses in never-lesional psoriasis skin

Publication date: Available online 27 September 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Irène Gallais Sérézal, Elena Hoffer, Borislav Ignatov, Elisa Martini, Beatrice Zitti, Marcus Ehrström, Liv Eidsmo

Abstract

Background

Resident T cells are implicated in the maintenance and recurrence of psoriasis lesions. Whether skin that has not yet experienced psoriasis in subjects with established disease harbours pathogenic T cells is less investigated.

Objective

To analyse the composition of resident T cells and T cell driven tissue responses in skin never affected by disease from psoriasis patients.

Methods

Never-lesional skin was collected from patients with mild psoriasis. T cell profiles were assessed with confocal imaging and flow cytometry. Tissue responses to T cell stimulation were measured by multiplex and Nanostring.

Results

T cell activation ex vivo triggered psoriasiform and type-I interferon tissue responses in epidermis from never-lesional psoriasis. Accordingly, keratinocytes from never-lesional psoriasis responded to IFN-γ stimulation with MX1 expression and IFN-α release. Additionally, CCR6 expressing resident T cells poised to produce IFN-γ and IL-17 were enriched in never-lesional epidermis whereas dermal tissue responses and T cell compositions were similar to healthy skin. Finally, never-lesional keratinocytes exposed to IL-17 and skin explants exposed to common fungal antigens responded with upregulation of the CCR6-ligand CCL20.

Conclusion

Epidermal resident T cells capable of triggering psoriasiform tissue responses accumulate in never-lesional epidermis. Our global analysis of never-lesional psoriasis reveals that microbial interplay with genetically predisposed keratinocytes may shape the local pool of resident T cells.

Graphical abstract

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