title: Involvement of interleukin-21 in the pathophysiology of aplastic anemia.
abstract: OBJECTIVE
  Recently enhanced T-helper type 17 (Th17) immune responses and deficient CD4(+) CD25(hi) FoxP3(+) regulatory T cells (Tregs) have been reported in acquired aplastic anemia (AA). Interleukin-21 (IL-21), a CD4(+) T-cell-derived proinflammatory cytokine, modulates the balance between Th17 cells and Tregs. However, its role in AA remains unclear.
  
  
  METHODS
  IL-21 gene expression was examined by quantitative real-time PCR. Cytokines in plasma and cell culture supernatants were detected by ELISA. Cytokines-producing T cells and Tregs were evaluated by flow cytometry.
  
  
  RESULTS
  IL-21 mRNA levels in circulating CD4(+) T cells and IL-21 levels in blood plasma were markedly increased in patients with newly diagnosed AA. Moreover, elevated IL-21-producing CD4(+) T cells were accompanied by Th17 cells accumulation and Tregs decrease, and correlated with AA activity. In vitro, IL-21 not only inhibited the expression of FoxP3, but also induced the expression of IL-17 in CD4(+) T cells of AA patients. More importantly, we found that T cells within the bone marrow (BM) of AA patients were in a heightened activation state, which may be related to IL-21.
  
  
  CONCLUSIONS
  Our data suggested a critical role of IL-21 in breaking immune homeostasis in AA by promoting Th17 cells, activating BM T cells and suppressing Tregs.
authors.affiliation: Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
authors.forename: Jizhou
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
authors.forename: Meili
authors.initials: M
authors.lastname: Ge
authors.affiliation: Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
authors.forename: Xingxin
authors.initials: X
authors.lastname: Li
authors.affiliation: Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Yao
authors.affiliation: Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology*; D000098546:Interleukin-21
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007378:Interleukins; D012333:RNA, Messenger; D000098546:Interleukin-21
keywords: CD69; Th17 cells; aplastic anemia; interleukin-21; regulatory T cells