Platelet-activating factor induces Th17 cell differentiation.
Th17 cells have been implicated in a number of inflammatory and autoimmune diseases. The phospholipid mediator platelet-activating factor (PAF) is found in increased concentrations in inflammatory lesions and has been shown to induce IL-6 production. We investigated whether PAF could affect the development of Th17 cells. Picomolar concentrations of PAF induced IL-23, IL-6, and IL-1β expression in monocyte-derived Langerhans cells (LCs) and in keratinocytes. Moreover, when LC were pretreated with PAF and then cocultured with anti-CD3- and anti-CD28-activated T cells, the latter developed a Th17 phenotype, with a significant increase in the expression of the transcriptional regulator RORγt and enhanced expression of IL-17, IL-21, and IL-22. PAF-induced Th17 development was prevented by the PAF receptor antagonist WEB2086 and by neutralizing antibodies to IL-23 and IL-6R. This may constitute a previously unknown stimulus for the development and persistence of inflammatory processes that could be amenable to pharmacologic intervention.
Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
Anne-Marie
AM
Drolet
Maryse
M
Thivierge
Sylvie
S
Turcotte
Dominique
D
Hanna
Bruno
B
Maynard
Jana
J
Stankovà
Marek
M
Rola-Pleszczynski
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D058504:Th17 Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D010972:Platelet Activating Factor