Interleukin-17-producing t-helper cells as new potential player mediating graft-versus-host disease in patients undergoing allogeneic stem-cell transplantation

Erica Dander, Adriana Balduzzi, Greta Zappa, Giovanna Lucchini, Paolo Perseghin, Valentina André, Elisabetta Todisco, Daoud Rahal, Maddalena Migliavacca, Daniela Longoni, Graziella Solinas, Antonello Villa, Emilio Berti, Pamela Della Mina, Matteo Parma, Paola Allavena, Ettore Biagi, Attilio Rovelli, Andrea Biondi, Giovanna Dĝamico

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVES: Graft-versus-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem-cell transplantation, leading to significant mortality. Recently, T-helper (TH)-17 cells have been shown to play a central role in mediating several autoimmune diseases. The aim of our study was to investigate the relationship between TH-17 cells and GVHD occurring in transplanted patients. METHODS: Blood samples were collected from 51 hematopoietic stem-cell transplantation patients and 15 healthy donors. Patients with GVHD were monitored for the presence of TH-17 cells by ELISPOT or flow cytometry in the peripheral blood and by confocal microscopy in GVHD lesions. Cytokine plasma levels were detected by ELISA. RESULTS: An increased TH-17 population (up to 4.8% of peripheral blood CD4+T lymphocytes) was observed in patients with acute GVHD and (up to 2.4%) in patients with active chronic GVHD along with an inflammatory process. In contrast, the percentage of TH-17 cells drastically decreased in patients with inactive chronic GVHD. TH-17 cells consisted of both interleukin (IL)-17/interferon (IFN)-γ3 and IL-17/IFN-γ3 subsets and expressed IL-23 receptor. Interestingly, IFN-γ3TH-17 cells were able to infiltrate GVHD lesions as observed in liver and skin sections. Moreover, the proportion of TH-17 was inversely correlated with the proportion of regulatory T cells observed in the peripheral blood and tissues affected by GVHD. Finally, we demonstrated a strong correlation between TH-17 levels and the clinical status of patients with GVHD. CONCLUSIONS: These findings support the hypothesis that TH-17 are involved in the active phases of GVHD and may represent a novel cellular target for developing new strategies for GVHD treatment.

Original languageEnglish
Pages (from-to)1261-1272
Number of pages12
JournalTransplantation
Volume88
Issue number11
DOIs
Publication statusPublished - Dec 2009

Keywords

  • GVHD
  • TH-17 cells
  • Transplantation

ASJC Scopus subject areas

  • Transplantation

Fingerprint Dive into the research topics of 'Interleukin-17-producing t-helper cells as new potential player mediating graft-versus-host disease in patients undergoing allogeneic stem-cell transplantation'. Together they form a unique fingerprint.

Cite this