IL-35 inhibits acute graft-versus-host disease in a mouse model.
Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our previous study found that the novel anti-inflammatory cytokine IL-35 could suppress aGVHD in patients after allo-HSCT. In this study, we used C57BL/6 (B6, H-2b) mice as donors and (B6×DBA/2) F1 (BDF1, H-2b×d) mice as recipients to create a model of aGVHD and explore the relationship between IL-35 and aGVHD. The mice receiving IL-35 survived longer than did the control mice. We observed that treatment with IL-35 and RAPA could reduce the incidence of aGVHD. Additionally, this treatment inhibited intestinal and thymic epithelial cell apoptosis and liver infiltration by the donor T-cells, thereby ameliorating the enteropathy and liver injury caused by aGVHD. We found that IL-35 and RAPA also markedly suppressed TNF-α and IL-17A expression and enhanced IFN-γ expression in the intestine and liver. We measured Tregs in spleen and found that IL-35 and RAPA treatment expanded the number of Tregs in spleen. We found that the phosphorylation of STAT1 and STAT4 were inhibited in mice with aGVHD. In contrast, STAT1 and STAT4 were phosphorylated when the mice were treated with IL-35. IL-35 may have therapeutic potential in the treatment of aGVHD after allo-HSCT.
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, China. Electronic address: zhangxh100@sina.com.
Xiao-Hui
XH
Zhang
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Yi
Y
Zhou
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Jia-Min
JM
Zhang
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, China.
Shi-Yuan
SY
Zhou
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Min
M
Wang
Department of Hematology, Beijing Hospital, Ministry of Health, Beijing, China.
Ru
R
Feng
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Fer-Er
FE
Feng
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Qian-Ming
QM
Wang
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Xiao-Lu
XL
Zhu
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Xiao-Su
XS
Zhao
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Meng
M
Lv
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Yuan
Y
Kong
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Ying-Jun
YJ
Chang
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, China.
Xiao-Jun
XJ
Huang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007378:Interleukins / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D020123:Sirolimus / Q000627:therapeutic use; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000187:drug effects
D016207:Cytokines; D007166:Immunosuppressive Agents; D007378:Interleukins; C569375:interleukin-35, mouse; D020123:Sirolimus
Acute graft-versus-host disease; Bone marrow transplantation; IL-35; Rapamycin