title: Interleukin-27 enhances the production of tumour necrosis factor-α and interferon-γ by bone marrow T lymphocytes in aplastic anaemia.
abstract: Aplastic anaemia (AA) is considered as an immune-mediated bone marrow failure syndrome. The mechanism is involved with a variety of immune molecules including interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) and interleukins (ILs). IL-27 is a novel member of the IL-12 family, which mediates T cell response and enhances the production of IFN-γ. However, little is known about the role of IL-27 in the development of AA. This study investigated the role of IL-27 and its receptor IL-27R in the pathogenesis of AA. Both the mRNA expression of IL-27/IL-27R subunits in the bone marrow mononuclear cells (BMMNCs) and the levels of IL-27 in the marrow plasma in AA were found to be higher than in controls. Increased IL-27 correlated with the disease severity of AA. Subsequently, we stimulated marrow T lymphocytes with recombinant human (rh)IL-27 and found that rhIL-27 enhanced the production of TNF-α and IFN-γ in both CD4(+) and CD8(+) T lymphocytes from AA patients. We also detected increased TNF-α and IFN-γ in the supernatants of BMMNCs from AA patients after IL-27 stimulation. In conclusion, our data suggest that elevated IL-27 and IL-27-induced TNF-α and IFN-γ overproduction might be involved in the pathogenesis of AA.
authors.affiliation: State Key Laboratory of Experimental Haematology, Institute of Haematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Li
authors.forename: Qinjun
authors.initials: Q
authors.lastname: Zhao
authors.forename: Wen
authors.initials: W
authors.lastname: Xing
authors.forename: Jianming
authors.initials: J
authors.lastname: Feng
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Li
authors.forename: Meili
authors.initials: M
authors.lastname: Ge
authors.forename: Kun
authors.initials: K
authors.lastname: Tian
authors.forename: Xingxin
authors.initials: X
authors.lastname: Li
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Zheng
authors.forename: Zhong C
authors.initials: ZC
authors.lastname: Han
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: C097732:EBI3 protein, human; C112441:IL27RA protein, human; C494199:IL6ST protein, human; D020381:Interleukin-17; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D014409:Tumor Necrosis Factor-alpha; D050822:Cytokine Receptor gp130; D007371:Interferon-gamma