Primary human keratinocytes efficiently induce IL-1-dependent IL-17 in CCR6+ T cells.
Keratinocytes and activated T cells interact in skin inflammation by virtue of chemokines and cytokines. T cell-derived IL-17 has been described to play an important role in the course of psoriatic inflammation. In this study, we addressed how keratinocytes influence the secretion of IL-17 in autologous T cell subsets. We found that a co-culture of autologous keratinocytes and T cell-receptor-stimulated T cells markedly enhanced the production of IL-17. Besides the importance of direct cell contact, this effect was mainly mediated by IL-1 and could be blocked by the IL-1 antagonist anakinra. An additional increase in IL-17 production by IL-23 was only seen in the presence of IL-1, which thus plays a permissive role for the action of IL-23. Importantly, co-culture of keratinocytes with CCR6+ CD4+ T cells that are enriched for Th17 cells resulted in significantly higher IL-17 production compared to co-culture with CD4+ T cells.
Muhr
Philipp
P
Renne
Julius
J
Schaefer
Verena
V
Werfel
Thomas
T
Wittmann
Miriam
M
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D020381:Interleukin-17 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D053759:Interleukin-23 / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D054399:Receptors, CCR6 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D000906:Antibodies; C106311:CCR6 protein, human; D017252:CD3 Complex; D017077:Culture Media, Conditioned; C508717:IL17A protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D054399:Receptors, CCR6; D011994:Recombinant Proteins