title: Pathological crosstalk in vitro between T lymphocytes and lesional keratinocytes in psoriasis: necessity of direct cell-to-cell contact.
abstract: Psoriasis, a chronic autoimmune-related skin disease, involves both immune and non-immune cells like T cells and keratinocytes. This study investigates the regulatory role of T cells-keratinocyte interactions during psoriasis on immune factors production. Cytokines and chemokines were evaluated by multiplex and ELISA assays in an in vitro model of co-culture of keratinocytes with T lymphocytes. Keratinocytes were from psoriatic skin lesions or healthy skin. T lymphocytes were from healthy volunteers. Psoriatic keratinocytes (PKs) alone generated concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-8, monocyte chemotactic protein (MCP)-1, interferon-γ-induced protein 10 kDa (IP-10) and vascular endothelial growth factor (VEGF) higher than those produced by healthy keratinocytes (HKs). In contrast, IL-1α and IL-Ra production was reduced in PKs. Normal T cells, which had no effect on HKs, increased the production of TNF-α, IL-6, GM-CSF, IL-8, MCP-1 and IP-10 by PKs, but did not influence PK production of IL-1β, IL-1α, IL-Ra and VEGF. The most striking effects were obtained with PK- and IL-2-stimulated T lymphocytes: most of the above cytokines and chemokines were greatly upregulated, except IL-1β and VEGF that were decreased or unchanged, respectively. In addition, fractalkine was overproduced in this latter condition only. Our results indicate (1) a functional interaction between keratinocytes and T lymphocytes that requires a direct cellular contact, and (2) a reciprocal influence that depends on cytokine and chemokine types. In conclusion, lesional keratinocytes from psoriasis vulgaris alter functions of normal T lymphocytes that conversely modulate these keratinocytes.
authors.affiliation: Laboratoire d'Organogénèse Expérimentale, Québec, QC, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Martin
authors.forename: Simon
authors.initials: S
authors.lastname: Guérard
authors.forename: Marie-Michèle Rosa
authors.initials: MM
authors.lastname: Fortin
authors.forename: Daniel
authors.initials: D
authors.lastname: Rusu
authors.forename: Jacques
authors.initials: J
authors.lastname: Soucy
authors.forename: Patrice E
authors.initials: PE
authors.lastname: Poubelle
authors.forename: Roxane
authors.initials: R
authors.lastname: Pouliot
mesh_terms: D002450:Cell Communication / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D015603:Keratinocytes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D018925:Chemokines; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007376:Interleukin-2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A