IL7 receptor signaling in T cells: A mathematical modeling perspective.
IL7 receptor signaling in T cells: A mathematical modeling perspective.
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T 细胞中的 IL7 受体信号传导：数学建模视角。
DOI：
10.1002/wsbm.1447
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Molina-París,Carmen
中科院分区：
文献类型：
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作者：
Park,Jung-Hyun;Waickman,AdamT;Reynolds,Joseph;Castro,Mario;Molina-París,Carmen
白细胞介素-7（IL-7）在T细胞存活和稳态中发挥非冗余作用，这在IL-7缺陷小鼠的严重T细胞淋巴细胞减少症中得到了说明，或者在缺乏IL-7 R α或γ c链（构成功能性IL-7受体的两个亚基）表达的动物或人类中得到了证明。值得注意的是，IL 7不是由T细胞本身表达的，而是由抗辐射基质细胞产生的有限数量。因此，T细胞需要不断竞争IL 7才能生存。T细胞如何在这种竞争中保持体内平衡并进一步最大化外周T细胞池的大小是免疫学家和数学家长期以来一直着迷的重要问题。例外的是，IL 7下调其自身受体的表达，使得IL 7信号传导的T细胞不消耗细胞外IL 7，因此，剩余的细胞外IL 7可以在未信号传导的T细胞之间共享。IL 7 R α链的这种利他行为在γ c细胞因子受体家族成员中是非常独特的。然而，这种利他信号行为在分子、单细胞和群体水平上的后果还不太清楚，需要进一步研究。在这方面，如何共享有限资源的数学建模，同时保持T细胞库的克隆多样性，可以帮助破译调节T细胞稳态的分子或细胞机制。因此，目前的审查旨在提供一个数学建模的角度，IL 7依赖的T细胞稳态在分子，细胞和群体水平，在最近的进展，我们的背景下，在我们的理解IL 7 biology.This文章分类下：模型的系统属性和过程>器官，组织和生理模型生物机制>细胞信号模型的系统属性和过程>机制模型分析和计算方法>计算方法
Interleukin‐7 (IL7) plays a nonredundant role in T cell survival and homeostasis, which is illustrated in the severe T cell lymphopenia of IL7‐deficient mice, or demonstrated in animals or humans that lack expression of either the IL7Rαorγcchain, the two subunits that constitute the functional IL7 receptor. Remarkably, IL7 is not expressed by T cells themselves, but produced in limited amounts by radio‐resistant stromal cells. Thus, T cells need to constantly compete for IL7 to survive. How T cells maintain homeostasis and further maximize the size of the peripheral T cell pool in face of such competition are important questions that have fascinated both immunologists and mathematicians for a long time. Exceptionally, IL7 downregulates expression of its own receptor, so that IL7‐signaled T cells do not consume extracellular IL7, and thus, the remaining extracellular IL7 can be shared among unsignaled T cells. Such an altruistic behavior of the IL7Rαchain is quite unique among members of theγccytokine receptor family. However, the consequences of this altruistic signaling behavior at the molecular, single cell and population levels are less well understood and require further investigation. In this regard, mathematical modeling of how a limited resource can be shared, while maintaining the clonal diversity of the T cell pool, can help decipher the molecular or cellular mechanisms that regulate T cell homeostasis. Thus, the current review aims to provide a mathematical modeling perspective of IL7‐dependent T cell homeostasis at the molecular, cellular and population levels, in the context of recent advances in our understanding of the IL7 biology.This article is categorized under:Models of Systems Properties and Processes > Organ, Tissue, and Physiological ModelsBiological Mechanisms > Cell SignalingModels of Systems Properties and Processes > Mechanistic ModelsAnalytical and Computational Methods > Computational Methods