An absence of donor TH17 differentiation ameliorates dermal tissue damage

Abstract

To explore the functions of TH17 cell in cutaneous graft-versus-host disease (GVHD). A model of acute GVHD (aGVHD) was established with a major histocompatibility complex class I/II-disparate allogeneic bone marrow transplantation (BMT). Bone marrow monocytes and splenic T cells from donor C57/BL6 were enriched. The recipient BABL mice were irradiated ((60)Co source) with 7.5 Gy total body irradiation (TBI) and injected with 5 × 10(6) marrow monocytes and 5 × 10(5) T cells. The experimental mice were divided into 3 groups: lethal total body irradiation (TBI); allogeneic bone marrow transplantation (BMT) and recipients of halofuginone (HF). The symptoms of aGVHD were observed daily and detailed histopathologic analyses of recipient skin were performed at Day 6 post-transplantation. And Tri-color flow cytometry (FCM) was performed at Day 6 post-transplantation to measure the levels of interleukin (IL)-17, interferon (IFN)-γ and TH1/TH17. Clinical GVHD symptoms were observed in recipient mice. The administration of HF to lethally irradiated recipients led to very modest GVHD-induced cutaneous changes manifested predominantly by fur loss. However, the experimental animals receiving only allogeneic BMT showed significant fur loss and pathologic skin conditions. Consistent with the clinical evaluations, the histopathologic results demonstrated significantly increased pathologic cutaneous lesions in recipients undergoing only BMT. The median ratios of TH1/TH17 cells were 17.57 and 5.31 in the HF and BMT groups respectively. The difference had statistical significance (P < 0.05). The serum levels of IL-17 were(1.47 ± 0.18) and (2.81 ± 0.19) pg/ml in the TBI and BMT groups respectively (P < 0.05). But IL-17 could not be detected in the HF group. The serum levels of IFN-γ were (3.86 ± 0.32), (42.97 ± 0.42) and (9.89 ± 0.51) pg/ml in the TBI, BMT and HF groups respectively. The inter-group differences had statistical significance (P < 0.05). An absence of TH17 cell may alleviate the cutaneous GVHD but exacerbate the systemic GVHD.