Increased TSLP availability restores T- and B-cell compartments in adult IL-7-deficient mice
Increased TSLP availability restores T- and B-cell compartments in adult IL-7-deficient mice
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DOI：
10.1182/blood-2007-02-074245
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发表时间：
2007-12-01
期刊：
影响因子：
20.3
通讯作者：
Finke, Daniela
中科院分区：
文献类型：
--
作者：
Chappaz, Stephane;Flueck, Lukas;Finke, Daniela
白细胞介素7（IL-7）在成人淋巴细胞生成中起着至关重要的作用，而在胎儿期，它的作用可以部分地被TSLP所补偿。在这里，我们表明，通过转基因（Tg）表达增加TSLP的可用性完全恢复了IL-7缺陷小鼠的淋巴细胞生成：它拯救了B细胞发育，增加了胸腺和脾脏细胞，并恢复了双阴性（DN）胸腺细胞，α β和γ δ T细胞生成，以及所有外周淋巴细胞。骨髓嵌合体的分析表明，造血祖细胞从成年野生型小鼠有效地分化向B-和T-细胞谱系在致死辐射的IL-7缺陷型小鼠提供TSLP Tg表达在这些小鼠。体外实验表明TSLP可促进未定型成人骨髓祖细胞向B、T细胞分化，并促进胸腺细胞向DN 1、DN 2分化。总之，我们的研究结果表明，成人造血细胞是TSLP响应和TSLP可以维持长期的成人淋巴细胞生成。
Interleukin 7 (IL-7) plays a crucial role in adult lymphopoiesis, while in fetal life its effect can be partially compensated by TSLP Whether adult hematopoietic progenitor cells are unresponsive to TSLP or whether TSLP is less available in adult microenvironments is still a matter of debate. Here, we show that increased TSLP availability through transgene (Tg) expression fully restored lymphopoiesis in IL-7-deficient mice: it rescued B-cell development, increased thymic and splenic cellularities, and restored double-negative (DN) thymocytes, alpha beta and gamma delta T-cell generation, and all peripheral lymphold compartments. Analysis of bone marrow chimeras demonstrated that hematopoletic progenitor cells from adult wild-type mice efficiently differentiated toward B- and T-cell lineages in lethally irradiated IL-7 deficient mice provided TSLP Tg was expressed in these mice. In vitro, TSLP promoted the differentiation of uncommitted adult bone marrow progenitors toward B and T lineages and the further differentiation of DN1 and DN2 thymocytes. Altogether, our results show that adult hematopoietic cells are TSLP responsive and that TSLP can sustain long-term adult lymphopoiesis.