Streptococcus pyogenes–induced cutaneous lymphocyte antigen–positive T cell–dependent epidermal cell activation triggers TH17 responses in patients with guttate psoriasis - 04/08/16
Abstract |
Background |
Guttate psoriasis (GP) is characterized by acute onset of small, rounded psoriatic lesions. Although this particular phenotype of psoriasis is usually associated with streptococcal throat infections and mainly occurs in HLA-Cw6+ patients, the specific immunologic response to this innate stimulus that causes these skin lesions is poorly understood.
Objective |
This study aims to elucidate how key cellular elements of patients with GP respond to Streptococcus pyogenes and whether this initial immune response is favored by the genetic and environmental background of these patients.
Methods |
Circulating memory T cells and autologous epidermal cells from samples from either patients with GP (n = 14) or healthy control subjects (n = 6) were cocultured ex vivo in the presence of an S pyogenes extract. Levels of the psoriasis-associated cytokines IL-17A, IL-17F, IFN-γ, TNF-α, IL-6, and IL-8 were determined. The expression of several genes with increased (DEFB4, S100A7, LCN2, IL36G, IL8, CXCL9, CXCL10, and CXCL11) or decreased (FLG and LOR) transcripts in psoriatic lesions was examined in keratinocytes treated with coculture supernatants.
Results |
When skin-homing effector memory cutaneous lymphocyte antigen–positive T cells were used in cocultures, a TH17-dominant response was observed, as reflected by the higher amounts of IL-17A and IL-17F than IFN-γ. Moreover, a higher TH17 response was observed in cells isolated from patients with flares associated with a streptococcal tonsillitis and with the HLA-Cw6 allele (cohort 1). In addition, in normal keratinocytes the supernatants from these cocultures induced an increase in IL-17–associated genes, such as DEFB4, S100A7, LCN2, IL36G, and IL8 but a decrease in FLG and LOR, thereby confirming the role of activated TH17 cells.
Conclusion |
This study reveals a dominant TH17 response of cutaneous lymphocyte antigen–positive T cells activated by epidermal cells and S pyogenes in patients with GP.
Le texte complet de cet article est disponible en PDF.Key words : TH17, streptococcal pharyngitis, guttate psoriasis, cutaneous lymphocyte antigen, HLA-Cw*0602
Abbreviations used : ASO, CLA, CLA+/Epi or CLA−/Epi, Ct, GP, SE
Plan
| Supported by ERDF grants from the Instituto de Salud Carlos III (PI09/2222 and PI13/01845 to L.F.S.-B., PI09/07811 to A.G.-A., and PI13/01716 to R.P.). L.F.S.-B. coordinated projects and grants. E.R.-R. was the recipient of a PhD fellowship from the Ministerio de Educación, Cultura y Deporte. |
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| Disclosure of potential conflict of interest: A. Giménez-Arnau serves on the board of Novartis, Genentech, URIACH Pharma, and Almirall; receives grant funding from Novartis and URIACH; and receives speakers' fees from Novartis, GlaxoSmithKline, and Leo Pharma. A. Celada receives research funding from the Spanish Ministry of Economy. L. F. Santamaria-Babí receives research funding from RDF grants from the Instituto de Salud Carlos III Ester Ruiz Romeu receives research funding from Ministerio de Educación, Cultura y Deporte. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 138 - N° 2
P. 491 - août 2016 Retour au numéro
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