Role of podoplanin in the high interleukin-17A secretion resulting from interactions between activated lymphocytes and psoriatic skin-derived mesenchymal cells

Autor:	Mélissa Noack, Ndiémé Ndongo-Thiam, Pierre Miossec
Rok vydání:	2016
Předmět:	0301 basic medicine medicine.medical_treatment CD3 Immunology Cell Communication Lymphocyte Activation Peripheral blood mononuclear cell Monocytes 03 medical and health sciences medicine Humans Psoriasis Immunology and Allergy Secretion Lymphocytes Membrane Glycoproteins biology Interleukin-17 T-cell receptor Interleukin hemic and immune systems Original Articles Fibroblasts Coculture Techniques 030104 developmental biology Cytokine Podoplanin Leukocytes Mononuclear biology.protein Cytokines Interleukin 17 Inflammation Mediators
Zdroj:	Clinical and Experimental Immunology. 186:64-74
ISSN:	1365-2249 0009-9104
DOI:	10.1111/cei.12830
Popis:	Summary In the context of psoriasis, T helper type 17 (Th17) cells infiltrate the inflammatory site and interact with local mesenchymal cells, including skin fibroblasts. The aim of this work was to study the interactions of skin-derived fibroblasts with peripheral blood mononuclear cells (PBMC) with a focus on the Th17 pathway and to identify a mechanism which leads to a high interleukin (IL)−17 secretion. A co-culture system between PBMC and skin fibroblasts was developed. Healthy and patient PBMC were added to non-lesional or lesional skin fibroblasts at a 5:1 ratio for 48 h in the presence or not of activation with phytohaemagglutinin (PHA). Monocytes were removed or not by adherence before the co-culture. An anti-podoplanin antibody was also used during the co-culture. Cytokine production (IL-8, IL-6, IL-1β and IL-17) was measured by enzyme-linked immunosorbent assay (ELISA) and cell staining (CD3, CD4, IL-17 and podoplanin) by flow cytometry. Without T cell receptor (TCR) activation, IL-8, IL-6 and IL-1β production increased in PBMC-fibroblast co-culture compared to PBMC alone. No additional effect was observed with TCR activation, with no difference in the Th17 cell percentage in activated-PBMC alone or co-cultured. Conversely, IL-17 production was increased highly only in co-cultures between control and patient activated-PBMC and skin fibroblasts. Removal of monocytes decreased cytokine production, notably that of IL-17. Addition of an anti-podoplanin antibody decreased IL-17 secretion by 60%. Interactions between resting PBMC and fibroblasts induce the IL-8, IL-6 and IL-1β production. PBMC activation and cell interactions are critical for a high IL-17 secretion. Podoplanin contributes largely to this massive IL-17 secretion.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68efccc843c5b10a1854e51adbe04491 https://doi.org/10.1111/cei.12830 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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