Spontaneous Intestinal Tumorigenesis in Apc (/Min+) Mice Requires Altered T Cell Development with IL-17A.
Spontaneous Intestinal Tumorigenesis in Apc (/Min+) Mice Requires Altered T Cell Development with IL-17A.
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DOI：
10.1155/2015/860106
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发表时间：
2015
影响因子：
4.1
通讯作者：
Bothwell AL
中科院分区：
文献类型：
--
作者：
Chae WJ;Bothwell AL
炎症性疾病的控制需要具有显著加塔-3表达的功能性调节性T细胞（Tcells）。在这里，我们解决的抑制作用，THEOTH对肠道肿瘤发生的Apc /Min+小鼠模型，类似于人类家族性腺瘤性息肉病（FAP）。Apc /Min+小鼠固有层中Foxp 3 + TATA的频率显著增加，但加塔-3表达降低。为了解决杂合Apc基因突变在TcB中的作用，我们产生了Foxp 3-Cre，Apc flox/+小鼠。在过继转移到Apc /Min+小鼠中后，来自这些小鼠的TclA有效抑制肿瘤发生，与野生型TclA相当，表明TclA中的杂合Apc基因突变不会诱导对肿瘤微环境的失控。体外产生的Apc /Min+ iTcl 4（诱导型Tcl 4）的连续转移未能抑制肠肿瘤发生，表明从Apc /Min+小鼠胸腺产生的幼稚CD 4 T细胞受损。我们还表明，过继转移的IL-17 A缺陷型Apc /Min+ TcR抑制肿瘤生长，表明IL-17 A对损害Apc /Min+ TcR的肿瘤消退功能至关重要。综上所述，我们的结果表明，功能性胸腺中的T细胞发育和IL-17 A控制Treg抑制Apc /Min+小鼠肠道肿瘤发生的能力。
The control of inflammatory diseases requires functional regulatory T cells (Tregs) with significant Gata-3 expression. Here we address the inhibitory role of Tregs on intestinal tumorigenesis in the Apc /Min+ mouse model that resembles human familial adenomatous polyposis (FAP). Apc /Min+ mice had a markedly increased frequency of Foxp3+ Tregs and yet decreased Gata-3 expression in the lamina propria. To address the role of heterozygous Apc gene mutation in Tregs, we generated Foxp3-Cre, Apc flox/+ mice. Tregs from these mice effectively inhibited tumorigenesis comparable to wild type Tregs after adoptive transfer into Apc /Min+ mice, demonstrating that the heterozygous Apc gene mutation in Tregs does not induce the loss of control over tumor microenvironment. Adoptive transfer of in vitro generated Apc /Min+ iTregs (inducible Tregs) failed to inhibit intestinal tumorigenesis, suggesting that naïve CD4 T cells generated from Apc /Min+ mice thymus were impaired. We also showed that adoptively transferred IL-17A-deficient Apc /Min+ Tregs inhibited tumor growth, suggesting that IL-17A was critical to impair the tumor regression function of Apc /Min+ Tregs. Taken together, our results suggest that both T cell development in a functional thymus and IL-17A control the ability of Treg to inhibit intestinal tumorigenesis in Apc /Min+ mice.
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影响因子：
3.7
作者：
Akimova T;Beier UH;Wang L;Levine MH;Hancock WW
通讯作者：
Hancock WW
DOI：
10.1084/jem.20081359
发表时间：
2008-12-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lathrop SK;Santacruz NA;Pham D;Luo J;Hsieh CS
通讯作者：
Hsieh CS
影响因子：
24.5
作者：
Betts G;Jones E;Junaid S;El-Shanawany T;Scurr M;Mizen P;Kumar M;Jones S;Rees B;Williams G;Gallimore A;Godkin A
通讯作者：
Godkin A
影响因子：
4.4
作者：
Kryczek, Ilona;Wu, Ke;Zou, Weiping
通讯作者：
Zou, Weiping
影响因子：
4.4
作者：
Gottschalk, Rachel A.;Corse, Emily;Allison, James P.
通讯作者：
Allison, James P.