Local IL-17 production and a decrease in peripheral blood regulatory T cells in an animal model of bronchiolitis obliterans

Abstract

Background: Recently, it has been reported that Th17 contributes to allograft rejection after transplantation. We investigated the alteration of Th17 and regulatory T cells (Treg) distribution in an animal model of bronchiolitis obliterans following ectopic tracheal transplantation model.

Methods: Tracheal grafts from B6 mice transplanted into subcutaneous sites of C3H mice. Allografts were histologically evaluated, and expressions of CD4, CD8, CD25, CD28, CD127, CD152 and Foxp3, and intracellular interleukin (IL)-4, -6, -17, and interferon-gamma, in peripheral blood lymphocytes were analyzed. Tracheal graft IL-6 and -17 mRNA expression was assessed using a quantitative reverse-transcriptase polymerase chain reaction. All the data in allogenic transplantation was compared with those in isograft controls. In addition, the effect of IL-6 neutralization on the allograft was evaluated with histopathology and the IL-17 mRNA expression.

Results: Treg was significantly lower in peripheral blood of allogenic mice, whereas no significant difference in Th17 in the CD4 T-cell population was observed after allogenic or isogenic transplantation. Locoregional histologic examination revealed the presence of IL-6-producing lymphocytes and endothelium in the allograft, and the luminal obliteration by fibroblast proliferation. Both IL-6 and IL-17 mRNA levels were elevated in the allograft. Severity of tracheal obliteration and IL-17 mRNA level was significantly suppressed in the IL-6 neutralized allografts.

Conclusions: After allograft in a mouse bronchiolitis obliterans model, IL-17 production increases locally without an alteration in peripheral blood Th17 cells, whereas peripheral Tregs decreases. Th17 cells, which can be regulated by IL-6 stimulation, may play a role in posttransplantation rejection of the allograft.