miRNA signature of mouse helper T cell hyper-proliferation.
miRNA signature of mouse helper T cell hyper-proliferation.
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DOI：
10.1371/journal.pone.0066709
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Samelson LE
中科院分区：
文献类型：
--
作者：
Sommers CL;Rouquette-Jazdanian AK;Robles AI;Kortum RL;Merrill RK;Li W;Nath N;Wohlfert E;Sixt KM;Belkaid Y;Samelson LE
来自突变小鼠模型 LAT Y136F 的辅助 T 细胞过度增殖并引起严重的淋巴增殖性疾病，导致小鼠在 6 个月大时死亡。 LAT Y136F 小鼠的 T 细胞激活连接子 (LAT) 基因中携带酪氨酸至苯丙氨酸突变。这种突变会导致 T 细胞发生许多变化，从而导致细胞因子产生改变，包括 IL-4 产生增加、增殖增加和细胞凋亡减少。突变 T 细胞的过度增殖导致淋巴结病、脾肿大和多器官 T 细胞浸润。 miRNA 是调节基因群表达的短非编码 RNA。本研究调查了哪些 miRNA 在 LAT Y136F T 细胞中表达，并将这些 miRNA 与在其他两种环境中进行增殖的野生型 T 细胞中表达的 miRNA 进行了比较。第一个设置是稳态增殖，通过将野生型 T 细胞过继转移到 T 细胞缺陷小鼠体内来建模。第二种情况是感染后的增殖，这是通过感染多回线虫的野生型小鼠来模拟的。通过将这三种增殖状态（LAT Y136F 过度增殖、稳态增殖和响应 H. Polygyrus 感染的增殖）中的 miRNA 表达与野生型幼稚 CD4+ T 细胞中的表达进行比较，我们发现在所有三种增殖状态（miR-21 和 miR-146a）中都受到高度调节的 miRNA，以及一些对个体增殖环境更具有特异性的 miRNA，例如针对 LAT Y136F 更具有特异性的 miRNA。淋巴组织增生性疾病（miR-669f、miR-155 和 miR-466a/b）。未来调节本研究中确定的 miRNA 水平的实验可能会揭示这些 miRNA 在 T 细胞增殖和/或淋巴增殖性疾病中的作用。
Helper T cells from a mutant mouse model, LAT Y136F, hyper-proliferate and cause a severe lymphoproliferative disease that kills the mice by six months of age. LAT Y136F mice carry a tyrosine to phenylalanine mutation in the Linker for Activation of T cells (LAT) gene. This mutation leads to a number of changes in T cells that result in altered cytokine production including increased IL-4 production, increased proliferation, and decreased apoptosis. Hyper-proliferation of the mutant T cells contributes to lymphadenopathy, splenomegaly, and multi-organ T cell infiltration. miRNAs are short non-coding RNAs that regulate expression of cohorts of genes. This study investigates which miRNAs are expressed in LAT Y136F T cells and compares these to miRNAs expressed in wild type T cells that are undergoing proliferation in two other settings. The first setting is homeostatic proliferation, which was modeled by adoptive transfer of wild type T cells into T cell-deficient mice. The second setting is proliferation in response to infection, which was modeled by infection of wild type mice with the nematode H. polygyrus. By comparing miRNA expression in these three proliferative states (LAT Y136F hyper-proliferation, homeostatic proliferation and proliferation in response to H. polygyrus infection) to expression in wild type naïve CD4+ T cells, we found miRNAs that were highly regulated in all three proliferative states (miR-21 and miR-146a) and some that were more specific to individual settings of proliferation such as those more specific for LAT Y136F lymphoproliferative disease (miR-669f, miR-155 and miR-466a/b). Future experiments that modulate levels of the miRNAs identified in this study may reveal the roles of these miRNAs in T cell proliferation and/or lymphoproliferative disease.
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DOI：
10.4049/jimmunol.1101235
发表时间：
2011-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lu TX;Hartner J;Lim EJ;Fabry V;Mingler MK;Cole ET;Orkin SH;Aronow BJ;Rothenberg ME
通讯作者：
Rothenberg ME
DOI：
10.1084/jem.20101074
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Grainger JR;Smith KA;Hewitson JP;McSorley HJ;Harcus Y;Filbey KJ;Finney CA;Greenwood EJ;Knox DP;Wilson MS;Belkaid Y;Rudensky AY;Maizels RM
通讯作者：
Maizels RM
影响因子：
4.4
作者：
Kortum, Robert L.;Rouquette-Jazdanian, Alexandre K.;Sommers, Connie L.
通讯作者：
Sommers, Connie L.
DOI：
10.1073/pnas.1112257109
发表时间：
2012-01-24
影响因子：
11.1
作者：
Cervo, Pia Rivetti di Val;Lena, Anna Maria;Melino, Gerry
通讯作者：
Melino, Gerry
影响因子：
11.1
作者：
Garchow, Barry G.;Encinas, Oscar Bartulos;Leung, Yiu Tak;Tsao, Patricia Y.;Eisenberg, Robert A.;Caricchio, Roberto;Obad, Susanna;Petri, Andreas;Kauppinen, Sakari;Kiriakidou, Marianthi
通讯作者：
Kiriakidou, Marianthi