Expression of IL-27, Th1 and Th17 in patients with aplastic anemia.
BACKGROUND
Aplastic anemia (AA) is an autoimmune disease and interleukin-27 (IL-27) is an important cytokine involved in the pathogenesis of autoimmune diseases. To date there have been no reports concerning the intrinsic association among IL-27 and Thelper (Th) 1 and Th17 cells in AA.


METHODS
Enzyme-linked immunosorbent assay (ELISA) to assay IL-27, interferon gamma (IFN-γ) and IL-17 levels, flow cytometry to measure the percentages of Th1 and Th17 cells among peripheral blood mononuclear cells (PBMCs), real-time reverse transcriptase polymerase chain reaction (PCR) for the mRNA levels of IL-27, IFN-γ, T-bet and IL-17 and retinoid related orphan receptor gamma (RORγt) in PBMCs were performed. In addition, the effect of exogenous rhIL-27 on the differentiation of T cells into Th1 and Th17 cells was investigated in vitro.


RESULTS
Plasma and mRNA levels of IL-27 in PBMCs from AA patients were significantly higher than those in healthy controls. A positive correlation was found between plasma levels of IL27 and IFN-γ. The proportions of Th1 and Th17 cells accompanied by the mRNA expression of RORγt and T-bet were significantly higher in AA patients than in healthy controls. Plasma levels of IL-27 correlated positively with frequencies of Th1 cells in AA patients. Exogenous rhIL-27 could significantly upregulate the frequency of Th1 cells and the mRNA levels of T-bet and IFN-γ and the application of rhIL-27 in vitro could inhibit the expression of RORγt mRNA.


CONCLUSIONS
The upregulation of IL-27 might cause Th1 differentiation and immune disorders in AA patients. Blocking the expression of IL-27 could therefore be a reasonable therapeutic strategy for AA.
Laiwu Central Hospital of Xinwen Mining Industry Group, Laiwu, Shandong, People's Republic of China.
Hui-zhen
HZ
Du
Qian
Q
Wang
Jian
J
Ji
Bao-ming
BM
Shen
Shao-chun
SC
Wei
Li-juan
LJ
Liu
Juan
J
Ding
Dao-xin
DX
Ma
Wen
W
Wang
Jun
J
Peng
Ming
M
Hou
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D020381:Interleukin-17 / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult; D000098815:T-bet Transcription Factor
D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma