Gimap3 and Gimap5 cooperate to maintain T-cell numbers in the mouse
Gimap3 and Gimap5 cooperate to maintain T-cell numbers in the mouse
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DOI：
10.1002/eji.201343750
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发表时间：
2014-02-01
影响因子：
5.4
通讯作者：
Takahama, Yousuke
中科院分区：
文献类型：
--
作者：
Yano, Kouta;Carter, Christine;Takahama, Yousuke
Gimap 3（IAN 4）和Gimap 5（IAN 5）是Gimap家族的高度同源的GTP结合蛋白。Gimap 3和Gimap 5在成熟淋巴细胞中大量转录，可与抗凋亡Bcl-2家族蛋白结合。虽然已经确定Gimap 5调节T细胞存活，但Gimap 3的体内作用尚不清楚。在这里，我们报告的准备和缺乏Gimap 3和/或Gimap 5的小鼠品系的特点。我们发现，在Gimap 3和Gimap 5缺陷的小鼠中，T细胞的数量显著减少。缺乏Gimap 3和Gimap 5的小鼠T细胞结构的缺陷比仅缺乏Gimap 5的小鼠更严重。在仅缺乏Gimap 3的小鼠中未检测到T细胞的细胞结构缺陷，而来自Gimap 3缺陷小鼠的骨髓细胞在竞争性造血环境中显示T细胞产生减少。此外，逆转录病毒过表达和短发夹RNA介导的Gimap 3在骨髓细胞中的沉默分别增加和减少了辐射小鼠中产生的T细胞的数量。这些结果表明，Gimap 3是小鼠T细胞数量的调节因子，并且多种Gimap家族蛋白协同维持T细胞存活。
Gimap3 (IAN4) and Gimap5 (IAN5) are highly homologous GTP-binding proteins of the Gimap family. Gimap3 and Gimap5, whose transcripts are abundant in mature lymphocytes, can associate with antiapoptotic Bcl-2 family proteins. While it is established that Gimap5 regulates T-cell survival, the in vivo role of Gimap3 is unclear. Here we report the preparation and characteristics of mouse strains lacking Gimap3 and/or Gimap5. We found that the number of T cells was markedly reduced in mice deficient in both Gimap3 and Gimap5. The defects in T-cell cellularity were more severe in mice lacking both Gimap3 and Gimap5 than in mice lacking only Gimap5. No defects in the cellularity of T cells were detected in mice lacking only Gimap3, whereas bone marrow cells from Gimap3-deficient mice showed reduced T-cell production in a competitive hematopoietic environment. Moreover, retroviral overexpression and short hairpin RNAs-mediated silencing of Gimap3 in bone marrow cells elevated and reduced, respectively, the number of T cells produced in irradiated mice. These results suggest that Gimap3 is a regulator of T-cell numbers in the mouse and that multiple Gimap family proteins cooperate to maintain T-cell survival.