TH17 cells are critical for skin-specific pathological injury in acute graft-versus-host disease.

Interleukin-17 (IL-17), which is important for host defens, has been implicated in autoimmune and chronic inflammatory diseases. As knockout mice lack IL-17 expression in δγT, NKT-like cells, studies investigating the association between TH17 cells and cutaneous graft-versus-host disease (GVHD) in animal models have reported conflicting results. To determine the role of TH17 cells in cutaneous GVHD, we developed an acute GVHD model using C57BL/6(H-2(b)) donors to BABL/c (H-2(d)) recipients. Blood samples and skin were examined for inflammation and infiltrating cells using histology and fluorescence-activated cell sorter (FACS) on days 6 and 15 after bone marrow transplantation. We found donor T cells to mediate severe cutaneous inflammation, which was ameliorater by administration of halofuginone (HF) to the recipients. Mechanistically, we demonstrate the severe tissue damage during this disorder to be associated with the production of IL-17 and the expansion of IL-17-producing CD4(+) cells. Specific inhibition of TH17 differentiation and function by HF reduced disease severity. Thus, TH17 cells are sufficient to induce acute cutaneous GVHD.

Cheng H ，Tian J ，Li Z ，Zeng L ，Pan B ，Song G ，Chen W ，Xu K ... -  《-》

Halofugine prevents cutaneous graft versus host disease by suppression of Th17 differentiation.

Cheng H ，Tian J ，Zeng L ，Pan B ，Li Z ，Song G ，Chen W ，Xu K ... -  《-》

Deviated balance between Th1 and Th17 cells exacerbates acute graft-versus-host disease in mice.

Th1/Th17 imbalance had been indicated to mediate several kinds of inflammatory diseases. We deduce that Th1/Th17 imbalance might also contribute to the pathogenesis of acute graft-versus-host disease (GVHD). This study is to investigate the relation between Th1/Th17 imbalance and acute GVHD. We applied a murine GVHD model of C57BL/6 (H-2(b)) donor to BALB/c (H-2(d)) recipient by treating the recipients with low dose of halofuginone (HF), which is competent in selectively inhibiting Th17 differentiation and facilitating Th1 differentiation. Recipient mice were monitored for survival rate, body weight change, clinical symptoms and pathological evidence of acute GVHD. We also measured the proportions of Th1 and Th17 cells in circulation and expression levels of IFN-γ and IL-17A in tissues involved in GVHD. Firstly, we confirm the existence of Th1/Th17 imbalance in acute GVHD and Th1/Th17 imbalance positively correlates with severity of acute GVHD. Secondly, low dose of HF augments Th1/Th17 imbalance by driving the Th1/Th17 balance to a Th1-dominant reaction. Finally, augmented Th1/Th17 imbalance leads to aggravated systemic GVHD. An increased Th1-type reaction results in aggravated hepatic and intestinal GVHD, and inhibiting Th17 differentiation is sufficient to alleviate pulmonic impairment. Our study is indicative for a critical role of Th1/Th17 imbalance in the pathogenesis of murine GVHD.

Pan B ，Zhang Y ，Sun Y ，Cheng H ，Wu Y ，Song G ，Chen W ，Zeng L ，Xu K ... -  《-》

[An absence of donor TH17 differentiation ameliorates dermal tissue damage].

Cheng H ，Song GL ，Pan B ，Tian J ，Yan ZL ，Chen W ，Xu KL ，Li ZY ，Zeng LY ... -  《-》

Interferon-gamma regulates idiopathic pneumonia syndrome, a Th17+CD4+ T-cell-mediated graft-versus-host disease.

Mauermann N ，Burian J ，von Garnier C ，Dirnhofer S ，Germano D ，Schuett C ，Tamm M ，Bingisser R ，Eriksson U ，Hunziker L ... -  《-》