Local IL-17 production and a decrease in peripheral blood regulatory T cells in an animal model of bronchiolitis obliterans.
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.
Nakagiri
Tomoyuki
T
Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan.
Inoue
Masayoshi
M
Morii
Eiichi
E
Minami
Masato
M
Sawabata
Noriyoshi
N
Utsumi
Tomoki
T
Kadota
Yoshihisa
Y
Ideguchi
Kan
K
Tokunaga
Toshiteru
T
Okumura
Meinoshin
M
D000818:Animals; D001989:Bronchiolitis Obliterans / Q000276:immunology* / Q000601:surgery; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002828:Choristoma / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014132:Trachea / Q000473:pathology / Q000637:transplantation*; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology
D018106:CD28 Antigens; D016207:Cytokines; D020381:Interleukin-17