T helper 9 (Th9) cells and interleukin (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) have not yet been studied adequately. IL-9, IL-9R, transcription factor PU.1 (PU.1), IL-4, thymic stromal lymphopoietin (TSLP) and transforming growth factor (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 analysed 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 observed mainly 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 among SSc peripheral blood mononuclear cells (PBMC), their percentage being correlated directly 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-systemic scleroderma 70 (Scl70) production by B cells. Our findings suggest that Th9 cells and IL-9 could be implicated in the pathogenesis of SSc.
Guggino, G., Lo Pizzo, M., Di Liberto, D., Rizzo, A., Cipriani, P., Ruscitti, P., et al. (2017). Interleukin-9 over-expression and T helper 9 polarization in systemic sclerosis patients. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 190.
|Data di pubblicazione:||2017|
|Titolo:||Interleukin-9 over-expression and T helper 9 polarization in systemic sclerosis patients.|
|Citazione:||Guggino, G., Lo Pizzo, M., Di Liberto, D., Rizzo, A., Cipriani, P., Ruscitti, P., et al. (2017). Interleukin-9 over-expression and T helper 9 polarization in systemic sclerosis patients. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 190.|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/cei.13009|
|Settore Scientifico Disciplinare:||Settore MED/16 - Reumatologia|
|Appare nelle tipologie:||1.01 Articolo in rivista|
File in questo prodotto:
|Guggino_et_al-2017-Clinical_&_Experimental_Immunology.pdf||N/A||Administrator Richiedi una copia|