IL-18 acts in synergy with IL-7 to promote ex vivo expansion of T lymphoid progenitor cells.
IL-18 acts in synergy with IL-7 to promote ex vivo expansion of T lymphoid progenitor cells.
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DOI：
10.4049/jimmunol.1301542
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发表时间：
2015-04-15
期刊：
影响因子：
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通讯作者：
Teague TK
中科院分区：
文献类型：
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作者：
Gandhapudi SK;Tan C;Marino JH;Taylor AA;Pack CC;Gaikwad J;Van De Wiele CJ;Wren JD;Teague TK
虽然IL-18以前没有被证明可以促进T淋巴细胞生成，但通过一种新的数据挖掘算法（GAMMA）获得的结果使我们探索了这种细胞因子在T细胞发育中的预测作用。IL-18是IL-1细胞因子家族的成员，已被广泛表征为炎症免疫反应的介质。为了评估IL-18在T细胞发育中的潜在作用，我们分选纯化小鼠骨髓衍生的共同淋巴样祖细胞（CLP）、早期胸腺祖细胞（ETP）和DN 2胸腺细胞，并在存在或不存在IL-18和/或IL-7的情况下在0 P9-DL 4基质层上培养这些群体。培养一周后，IL-18促进ETP增殖并加速其分化至DN 3期，其效率与IL-7相似。IL-18显示出与IL-7的协同作用，并增强了胸腺来源的祖细胞和骨髓来源的共同淋巴祖细胞的增殖。对ETP群体的协同效应被进一步表征，并发现与IL-18处理的细胞上c-Kit和IL-7受体的表面表达增加相关。总之，我们成功验证了Gamma预测，即IL-18影响T淋巴细胞生成，并证明IL-18可能通过与c-Kit和IL-7信号传导轴的相互作用对骨髓淋巴细胞生成和T细胞发育产生积极影响。
Although IL-18 has not previously been shown to promote T lymphopoiesis, results obtained via a novel data mining algorithm (GAMMA), led us to explore a predicted role for this cytokine in T cell development. IL-18 is a member of the IL-1 cytokine family that has been extensively characterized as a mediator of inflammatory immune responses. To assess a potential role for IL-18 in T cell development, we sort-purified mouse bone marrow derived common lymphoid progenitor cells (CLP), early thymic progenitors (ETP) and DN2 thymocytes and cultured these populations on OP9-DL4 stromal layers in the presence or absence of IL-18 and/or IL-7. After one week of culture, IL-18 promoted proliferation and accelerated differentiation of ETPs to the DN3 stage, similar in efficiency to IL-7. IL-18 showed synergy with IL-7 and enhanced proliferation of both the thymus derived progenitor cells and the bone marrow derived common lymphoid progenitor cells. The synergistic effect on the ETP population was further characterized and found to correlate with increased surface expression of c-Kit and IL-7 receptors on the IL-18-treated cells. In summary, we successfully validated the GAMMA prediction that IL-18 affects T lymphopoiesis and demonstrated that IL-18 can positively impact bone marrow lymphopoiesis and T cell development, presumably via interaction with the c-Kit and IL-7 signaling axis.