Interleukin-9 over-expression and T helper 9 polarization in systemic sclerosis patients.

Guggino, G; Lo Pizzo, M; Di Liberto, D; Rizzo, A; Cipriani, P; Ruscitti, P; Candore, G; Gambino, C M; Sireci, G; Dieli, F; Giacomelli, R; Triolo, G; Ciccia, F

Guggino, G; Lo Pizzo, M; Di Liberto, D; Rizzo, A; Cipriani, P; Ruscitti, P; Candore, G; Gambino, C M; Sireci, G; Dieli, F; Giacomelli, R; Triolo, G; Ciccia, F.

Afiliación

Guggino G; Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo, Palermo, Italy.
Lo Pizzo M; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
Di Liberto D; Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy.
Rizzo A; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
Cipriani P; Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy.
Ruscitti P; Azienda Ospedaliera Ospedali riuniti Villa Sofia-Cervello, Anatomia Patologica, Palermo, Italy.
Candore G; Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy.
Gambino CM; Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy.
Sireci G; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
Dieli F; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
Giacomelli R; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
Triolo G; Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy.
Ciccia F; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.

Clin Exp Immunol ; 190(2): 208-216, 2017 11.

Article en En | MEDLINE | ID: mdl-28681919

RESUMEN

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)-ß 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-ß 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.

Asunto(s)

Linfocitos T CD4-Positivos/inmunología; Interleucina-9/metabolismo; Esclerodermia Sistémica/inmunología; Adulto; Autoanticuerpos/sangre; Linfocitos B/efectos de los fármacos; Linfocitos T CD4-Positivos/clasificación; Linfocitos T CD4-Positivos/metabolismo; Diferenciación Celular; Citocinas/genética; Citocinas/metabolismo; Trampas Extracelulares/metabolismo; Femenino; Humanos; Interleucina-4/genética; Interleucina-4/metabolismo; Interleucina-9/sangre; Interleucina-9/genética; Interleucina-9/inmunología; Masculino; Mastocitos/inmunología; Mastocitos/metabolismo; Persona de Mediana Edad; Neutrófilos/inmunología; Neutrófilos/metabolismo; Proteínas Proto-Oncogénicas/genética; Proteínas Proto-Oncogénicas/metabolismo; Receptores de Interleucina-9/genética; Receptores de Interleucina-9/metabolismo; Esclerodermia Sistémica/fisiopatología; Piel/inmunología; Piel/metabolismo; Piel/patología; Transactivadores/genética; Transactivadores/metabolismo; Factor de Crecimiento Transformador beta/genética; Factor de Crecimiento Transformador beta/metabolismo; Linfopoyetina del Estroma Tímico

Palabras clave

IL-9; ILC2; Th9; systemic sclerosis

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerodermia Sistémica / Linfocitos T CD4-Positivos / Interleucina-9 Tipo de estudio: Prognostic_studies Idioma: En Revista: Clin Exp Immunol Año: 2017 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido

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