IL-7 is essential for homeostatic control of T cell metabolism in vivo.
IL-7 is essential for homeostatic control of T cell metabolism in vivo.
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DOI：
10.4049/jimmunol.0902593
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发表时间：
2010-04-01
期刊：
影响因子：
--
通讯作者：
Rathmell JC
中科院分区：
文献类型：
--
作者：
Jacobs SR;Michalek RD;Rathmell JC
很明显，T细胞需要生长信号来维持维持适当的免疫平衡所必需的功能和活性。细胞外源信号调节这些效应的一种方法是维持足够的基础细胞代谢，以防止细胞萎缩。然而，在体内维持成熟T细胞新陈代谢所必需的代谢和特定的生长因子的作用尚不清楚。由于IL-7是T细胞发育和存活所必需的非冗余细胞因子，并且在体外可以调节T细胞的代谢，我们推测它可能是维持体内静止T细胞代谢所必需的。因此，我们建立了成熟T细胞条件表达IL-7R的模型。在一般正常的淋巴环境中，IL-7R缺失后，T细胞对IL-7的反应减弱，包括信号转导被取消，抗凋亡的Bcl-2家族表达维持，这对应于体外存活减少。体内T细胞存活率在失去IL-7R后也以T细胞固有的方式减少。此外，IL-7R缺失会导致刺激后的生长和增殖延迟。重要的是，在体内切除IL-7R会导致T细胞萎缩，其特征是有丝分裂延迟和糖酵解通量减少。这些数据首次确定了体内对维持淋巴细胞代谢的特定细胞外部信号的需求，并表明IL-7R对糖酵解的控制可能有助于IL-7在T细胞发育、体内平衡增殖和生存中的作用。
It has become apparent that T cells require growth signals to maintain function and viability necessary to maintain proper immune homeostasis. One means by which cell extrinsic signals may mediate these effects is by sustaining sufficient basal cell metabolism to prevent cell atrophy. The role of metabolism and the specific growth factors essential to maintain metabolism of mature T cells in vivo, however, are poorly defined. As IL-7 is a nonredundant cytokine required for T cell development and survival and can regulate T cell metabolism in vitro, we hypothesized it may be essential to sustain metabolism of resting T cells in vivo. Thus, we generated a model for conditional expression of IL-7R in mature T cells. After IL-7R deletion in a generally normal lymphoid environment, T cells had reduced responses to IL-7, including abrogated signaling and maintenance of antiapoptotic Bcl-2 family expression that corresponded to decreased survival in vitro. T cell survival in vivo was also reduced after loss of the IL-7R in a T cell-intrinsic manner. Additionally, IL-7R deletion resulted in delayed growth and proliferation following stimulation. Importantly, in vivo excision of IL-7R led to T cell atrophy that was characterized by delayed mitogenesis and reduced glycolytic flux. These data are the first to identify an in vivo requirement for a specific cell extrinsic signal to sustain lymphocyte metabolism and suggest that control of glycolysis by IL-7R may contribute to the well-described roles of IL-7 in T cell development, homeostatic proliferation, and survival.
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影响因子：
32.4
作者：
Alves, Nuno L.;Derks, Ingrid A. M.;Eldering, Eric
通讯作者：
Eldering, Eric
影响因子：
5.4
作者：
Rathmell, JC;Elstrom, RL;Thompson, CB
通讯作者：
Thompson, CB
DOI：
10.1084/jem.182.4.1101
发表时间：
1995-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Nakayama K;Nakayama K;Dustin LB;Loh DY
通讯作者：
Loh DY
影响因子：
64.5
作者：
Akashi, K;Kondo, M;Weissman, IL
通讯作者：
Weissman, IL
影响因子：
11.8
作者：
Edinger, AL;Cinalli, RM;Thompson, CB
通讯作者：
Thompson, CB