title: Interleukin 27 inhibits cytotoxic T-lymphocyte-mediated platelet destruction in primary immune thrombocytopenia.
abstract: Cytotoxic T-lymphocyte (CTL)-mediated platelet destruction and aberrant cytokine profiles play important roles in the pathogenesis of primary immune thrombocytopenia (ITP). Interleukin-27 (IL-27) has pleiotropic immunomodulatory effects. However, the effect of IL-27 on CTL activity in ITP has not been reported. In the present study, platelets from ITP patients were cultured with autologous CTLs in the presence of IL-27. We found that IL-27 could inhibit CTL-mediated platelet destruction. In these IL-27-treated CTLs, granzyme B and T-bet expression decreased significantly, whereas granzyme A, perforin, and eomesodermin were not affected. To further investigate the role of granzyme B in CTL-mediated platelet destruction, granzyme B inhibitor was added and platelet apoptosis was significantly inhibited. These results suggest that IL-27 negatively regulates CTL cytotoxicity toward platelets in ITP by decreasing granzyme B expression, which is associated with reduced T-bet expression. IL-27 may have a therapeutic role in treating ITP patients.
authors.affiliation: Department of Hematology.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Hematology.
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Qiu
authors.affiliation: Cancer Center, and.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Hematology.
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Yu
authors.affiliation: Department of Hematology.
authors.forename: Xue-Na
authors.initials: XN
authors.lastname: Liu
authors.affiliation: Department of Hematology.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Hematology.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Department of Hematology.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Hematology.
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Li
authors.affiliation: Cancer Center, and.
authors.forename: Xin-Guang
authors.initials: XG
authors.lastname: Liu
authors.affiliation: Department of Hematology, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
authors.affiliation: Department of Hematology, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets / Q000473:pathology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053804:Granzymes / Q000037:antagonists & inhibitors; D006801:Humans; D064094:Interleukin-27 / Q000494:pharmacology*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D064094:Interleukin-27; D053804:Granzymes