IL-9 over-expression and Th9 polarization in Systemic Sclerosis patients

Summary Th9 cells and IL-9 are involved in the pathogenesis of several autoimmune diseases. The exact role of IL-9 and Th9 cells in patients with Systemic Sclerosis (SSc) has not been yet adequately studied. IL-9, IL-9R, transcription factor PU.1 (PU.1), IL-4, thymic stromal lymphopoietin (TSLP) and TGF-β expression were assessed in skin and kidney biopsies of SSc patients and healthy controls (HC) by immunohistochemistry (IHC). The cellular source of IL-9 was also analyzed by confocal microscopy analysis. Peripheral IL-9-producing cells were also studied by flow cytometry. The functional relevance of IL-9 increased expression in SSc was also investigated. Our results demonstrated a strong expression of IL-9, IL-9R, IL-4, TSLP and TGF-β in skin tissues of patients with both limited and diffuse SSc. IL-9 expression was mainly observed in the context of skin infiltrating mononuclear cells and keratinizing squamous epithelium. IL-9 over-expression was also observed in renal biopsies of patients with SSc. IL-9 producing cells in the skin were identified as Th9 cells. Similarly, Th9 cells were expanded and were the major source of IL-9 amongst SSc peripheral blood mononuclear cells (PBMC) being their percentage directly correlated with the modified Rodnan skin score. Infiltrating mononuclear cells, mast cells and neutrophils expressed IL-9R. In in vitro studies stimulation with rIL-9 significantly induced NET (neutrophil extracellular traps) Release by Dying Cells (NETosis) in neutrophils, expansion of mast cells and increase of anti-Scl70 production by B cells. Our findings suggest that Th9 cells and IL-9 could be implicated in the pathogenesis of SSc. This article is protected by copyright. All rights reserved.