Interleukin 27 inhibits cytotoxic T-lymphocyte-mediated platelet destruction in primary immune thrombocytopenia.
Interleukin 27 inhibits cytotoxic T-lymphocyte-mediated platelet destruction in primary immune thrombocytopenia.
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白细胞介素 27 可抑制原发性免疫性血小板减少症中细胞毒性 T 淋巴细胞介导的血小板破坏。
DOI：
10.1182/blood-2014-06-580084
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发表时间：
2014-11
期刊：
影响因子：
20.3
通讯作者：
Peng, Jun
中科院分区：
文献类型：
--
作者：
Li, Li-Zhen;Liu, Xin-Guang;Hou, Ming;Peng, Jun
细胞毒性T淋巴细胞(CTL)介导的血小板破坏和细胞因子异常在原发免疫性血小板减少症(ITP)的发病机制中起重要作用。白介素27(IL-27)具有多效性免疫调节作用。然而，IL-27对ITP中CTL活性的影响尚未见报道。在本研究中，ITP患者的血小板与含有IL-27的自体CTL培养。我们发现IL-27可以抑制CTL介导的血小板破坏。在这些经IL-27处理的CTL中，颗粒酶B和T-bet的表达显著降低，而颗粒酶A、穿孔素和eomesodermin的表达不受影响。为了进一步研究颗粒酶B在CTL介导的血小板破坏中的作用，加入颗粒酶B抑制剂，并显著抑制了血小板的凋亡。这些结果表明，IL-27通过减少颗粒酶B的表达来负向调节ITP患者CTL对血小板的细胞毒作用，这与T-bet的表达减少有关。IL-27对ITP患者有一定的治疗作用。
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.
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影响因子：
20.3
作者：
Audia, Sylvain;Samson, Maxime;Bonnotte, Bernard
通讯作者：
Bonnotte, Bernard
影响因子：
--
作者：
Pickens, Sarah R.;Chamberlain, Nathan D.;Volin, Michael V.;Mandelin, Arthur M., II;Agrawal, Hemant;Matsui, Masanori;Yoshimoto, Takayuki;Shahrara, Shiva
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Shahrara, Shiva
影响因子：
30.5
作者：
Intlekofer, AM;Takemoto, N;Reiner, SL
通讯作者：
Reiner, SL
影响因子：
4.4
作者：
Diveu, Caroline;McGeachy, Mandy J.;Kastelein, Robert A.
通讯作者：
Kastelein, Robert A.
影响因子：
15.3
作者：
Juedes, AE;Rodrigo, E;Togher, L;Glimcher, LH;von Herrath, MG
通讯作者：
von Herrath, MG