Interleukin-11 induces Th2 polarization of human CD4+ T cells
Interleukin-11 induces Th2 polarization of human CD4+ T cells
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DOI：
10.1182/blood.v97.9.2758
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发表时间：
2001-05-01
期刊：
影响因子：
20.3
通讯作者：
Lemoli, RM
中科院分区：
文献类型：
--
作者：
Curti, A;Ratta, M;Lemoli, RM
对多功能细胞因子白细胞介素-11（IL-11）的免疫调节活性的探索已经促进了几种治疗应用。研究了IL-11对人抗原呈递细胞和T细胞的免疫调节作用。IL-11抑制活化的CD 14（+）单核细胞产生IL-12，但不抑制通过CD 40连接刺激的成熟树突状细胞（DC）产生IL-12。此外，IL-11不影响DC成熟，如表型分析和细胞因子产生的评价所示，或在特定生长因子存在下从祖细胞产生DC。分子分析证实了IL-11受体信使RNA在高度纯化的CD 14（+）单核细胞、CD 19（+）B细胞、CD 8（+）和CD 4（+）T细胞以及CD 4（+）CD 45 RA（+）初始T淋巴细胞中的表达，与这一发现一致，IL-11直接阻止用抗-CD 3/CD 28抗体刺激的高度纯化的CD 4（+）CD 45 RA（+）初始T细胞的Th 1极化，如通过IL-4和IL-5的显著增加所证明的，通过显著降低的干扰素-γ产生和通过流式细胞术细胞内细胞因子染色。幼稚T细胞与DC（Th 1分化的最有效刺激物）共孵育不能逆转IL-11介导的Th 2极化。此外，平行实验表明，IL-11的活性与最有效的Th 2极化细胞因子IL-4诱导的活性相当。总之，这些发现表明IL-11通过对人T淋巴细胞施加直接作用和通过减少巨噬细胞产生IL-12来抑制Th 1极化。相反，IL-11对DC不发挥任何活性。这表明IL-11可能对Th 1应答起主导致病作用的疾病具有治疗潜力。（血。2001;97：2758-2763）（C）2001由美国血液学学会。
Exploration of the immunomodulatory activities of the multifunctional cytokine interleukin-11 (IL-11) has prompted several therapeutic applications. The immunomodulatory effects of IL-11 on human antigen-presenting cells and on T cells were investigated. IL-11 inhibited IL-12 production by activated CD14(+) monocytes, but not by mature dendritic cells (DCs) stimulated via CD40 ligation. Moreover, IL-11 did not affect either DC maturation, as demonstrated by phenotypic analysis and evaluation of cytokine production, or DC generation from progenitor cells in the presence of specific growth factors. Molecular analysis demonstrated the expression of IL-11 receptor messenger RNA in highly purified CD14(+) monocytes, CD19(+) B cells, CD8(+), and CD4(+) T cells, and CD4(+) CD45RA(+) naive T lymphocytes, in keeping with this finding, IL-11 directly prevented Th1 polarization of highly purified CD4(+)CD45RA(+) naive T cells stimulated with anti-CD3/ CD28 antibodies, as demonstrated by significant increases of IL-4 and IL-5, by significantly decreased interferon-gamma production and by flow cytometry intracellular staining of cytokines. Coincubation of naive T cells with DCs, the most potent stimulators of Th1 differentiation, did not revert IL-11-mediated Th2 polarization. Furthermore, parallel experiments demonstrated that the activity of IL-11 was comparable with that induced by IL-4, the most effective Th2-polarizing cytokine. Taken together, these findings show that IL-11 inhibits Th1 polarization by exerting a direct effect on human T lymphocytes and by reducing IL-12 production by macrophages. Conversely, IL-11 does not exert any activity on DCs. This suggests that IL-11 could have therapeutic potential for diseases where Th1 responses play a dominant pathogenic role. (Blood. 2001;97:2758-2763) (C) 2001 by The American Society of Hematology.