Role of podoplanin in the high interleukin‐17A secretion resulting from interactions between activated lymphocytes and psoriatic skin‐derived mesenchymal cells. (9th August 2016)

• Record Type: Journal Article
• Authors: Noack, M.; Ndongo‐Thiam, N'D.; Miossec, P.
• Is Part Of: Clinical and experimental immunology. Volume 186:Number 1(2016:Oct.)
• Page Start: 64
• Page End: 74
• Publication Date: 2016-08-09
• Subjects: cell interactions -- IL‐17 -- immune cells -- podoplanin -- psoriasis -- skin fibroblasts; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12830
• Languages: English
• ISSNs: 0009-9104

Abstract

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.