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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Our study is indicative for a critical role of Th1/Th17 imbalance in the pathogenesis of murine GVHD.
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No. 99, West Huaihai Road, 221002 Xuzhou, China.
Bin
B
Pan
Laboratory of Transplant Immunology, Xuzhou Medical College, No. 84, West Huaihai Road, 221002 Xuzhou, China.
Ying
Y
Zhang
Laboratory of Transplant Immunology, Xuzhou Medical College, No. 84, West Huaihai Road, 221002 Xuzhou, China.
Yuqi
Y
Sun
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No. 99, West Huaihai Road, 221002 Xuzhou, China.
Hai
H
Cheng
Laboratory of Transplant Immunology, Xuzhou Medical College, No. 84, West Huaihai Road, 221002 Xuzhou, China.
Yujing
Y
Wu
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No. 99, West Huaihai Road, 221002 Xuzhou, China.
Guoliang
G
Song
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No. 99, West Huaihai Road, 221002 Xuzhou, China.
Wei
W
Chen
Laboratory of Transplant Immunology, Xuzhou Medical College, No. 84, West Huaihai Road, 221002 Xuzhou, China.
Lingyu
L
Zeng
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No. 99, West Huaihai Road, 221002 Xuzhou, China; Laboratory of Transplant Immunology, Xuzhou Medical College, No. 84, West Huaihai Road, 221002 Xuzhou, China. Electronic address: xukl_xzmc@163.com.
Kailin
K
Xu
D000208:Acute Disease; D000818:Animals; D018450:Disease Progression; D006086:Graft vs Host Disease / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D018655:Lymphocyte Count; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D052999:Quinazolinones / Q000008:administration & dosage / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
D020381:Interleukin-17; D010880:Piperidines; D052999:Quinazolinones; D007371:Interferon-gamma; C010176:halofuginone
Graft-versus-host disease; Th1 cell; Th17 cell