Chen Xi-Lin, Serrano Daniel, Mayhue Marian, Hoebe Kasper, Ilangumaran Subburaj, Ramanathan Sheela
Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, J1H 5N4, Québec, Canada.
Department of Pediatrics, Division of Cellular and Molecular Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States of America.
PLoS One. 2015 Oct 6;10(10):e0139019. doi: 10.1371/journal.pone.0139019. eCollection 2015.
Long-term survival of T lymphocytes in quiescent state is essential to maintain their cell numbers in secondary lymphoid organs. In mice and in rats, the loss of functional GTPase of the immune associated nucleotide binding protein 5 (GIMAP5) causes peripheral T lymphopenia due to spontaneous death of T cells. The underlying mechanism responsible for the disruption of quiescence in Gimap5 deficient T cells remains largely unknown. In this study, we show that loss of functional Gimap5 results in increased basal activation of mammalian target of rapamycin (mTOR), independent of protein phosphatase 2A (PP2A) or AMP-activated protein kinase (AMPK). Our results suggest that the constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway may be one of the consequences of the absence of functional GIMAP5.
静止状态下T淋巴细胞的长期存活对于维持其在次级淋巴器官中的细胞数量至关重要。在小鼠和大鼠中，免疫相关核苷酸结合蛋白5（GIMAP5）功能性GTP酶的缺失会导致外周T淋巴细胞减少，这是由于T细胞的自发死亡所致。Gimap5缺陷型T细胞中静止状态被破坏的潜在机制在很大程度上仍不清楚。在本研究中，我们表明功能性Gimap5的缺失导致雷帕霉素哺乳动物靶标（mTOR）的基础激活增加，这与蛋白磷酸酶2A（PP2A）或AMP激活的蛋白激酶（AMPK）无关。我们的结果表明，磷脂酰肌醇3激酶（PI3K）途径的组成性激活可能是缺乏功能性GIMAP5的后果之一。
