Anti-inflammatory effects of interleukin-35 in acquired aplastic anemia.
Interleukin (IL)-35 is a novel regulatory cytokine primarily produced by regulatory T cells. Accumulating evidence has established that IL-35 plays an important role in the regulation of immune homeostasis, but little is known regarding the function of IL-35 in acquired aplastic anemia (AA). The aim of the present study was to investigate the expression of IL-35 and its effects on T cell response in AA. Our study demonstrated that significantly decreased plasma levels of IL-35 in AA were closely correlated with disease severity. In vitro stimulation experiment further confirmed the anti-inflammatory effects of IL-35, including suppressing the proliferation of CD4(+) and CD8(+) effector T cells, inhibiting the secretion of interferon-γ, tumor necrosis factor-α and IL-17 and promoting the production of transforming growth factor-β by peripheral blood mononuclear cells from patients with AA. Furthermore, we established that IL-35 inhibited the differentiation of type 1 T cells and T helper 17 cells but promoted the differentiation of type 2 T cells. Accordingly, the expression of T-bet and RORγt was inhibited while the expression of GATA3 was induced after IL-35 treatment. In summary, our findings suggested that decreased IL-35 might contribute to the loss of immune-tolerance and be critically involved in the pathogenesis of AA.
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Wei
W
Yu
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Meili
M
Ge
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Shihong
S
Lu
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Jun
J
Shi
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Xingxin
X
Li
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Jizhou
J
Zhang
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Min
M
Wang
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Jinbo
J
Huang
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Yingqi
Y
Shao
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Zhendong
Z
Huang
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Jing
J
Zhang
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Neng
N
Nie
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China. Electronic address: zheng_yizhou@hotmail.com.
Yizhou
Y
Zheng
D000328:Adult; D000741:Anemia, Aplastic / Q000503:physiopathology*; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007378:Interleukins / Q000097:blood / Q000235:genetics / Q000502:physiology*; D008297:Male; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
D016207:Cytokines; D007378:Interleukins; D012333:RNA, Messenger; C532417:interleukin-35, human
Aplastic anemia; Bone marrow failure; Interleukin-35; Regulatory T cells; T helper cells