Insights into the role of Bcl6 in follicular Th cells using a new conditional mutant mouse model.
Insights into the role of Bcl6 in follicular Th cells using a new conditional mutant mouse model.
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DOI：
10.4049/jimmunol.1300378
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发表时间：
2013-10-01
期刊：
影响因子：
--
通讯作者：
Dent AL
中科院分区：
文献类型：
--
作者：
Hollister K;Kusam S;Wu H;Clegg N;Mondal A;Sawant DV;Dent AL
转录抑制因子Bcl 6控制滤泡辅助性T细胞（TFH）谱系的发育，然而Bcl 6调节该过程的精确机制尚不清楚。已经提出了一种模型，其中Bcl 6抑制T细胞分化成替代效应谱系，从而有利于TFH分化。使用Bcl 6缺陷型小鼠的T细胞分化的分析由于Bcl 6缺陷型骨髓细胞的强促炎表型而变得复杂。在这里，我们报告了一种新的小鼠模型的数据，其中Bcl 6在T细胞（Bcl 6 fl/flCreCD 4小鼠）中条件性缺失。免疫后，与对照小鼠相比，Bcl 6 fl/flCreCD 4小鼠中的PD-1 high TFH细胞减少了90%以上，抗原特异性IgG急剧减少。Bcl 6 fl/flCreCD 4小鼠中残留的PD-1高CXCR 5 + TFH细胞显示出比对照小鼠中PD-1高CXCR 5 + TFH细胞显著更高的凋亡率。Bcl 6 fl/flCreCD 4小鼠的免疫没有显示向TH 1、TH 2或TH 17谱系的分化增强，尽管CD 4 T细胞的IL-10表达显著升高。因此，T细胞外在因子似乎促进生殖系Bcl 6缺陷小鼠中增加的TH 1、TH 2和TH 17应答。此外，IL-10可能是Bcl 6在CD 4 T细胞中的关键靶基因，其使得Bcl 6能够促进TFH细胞表型。最后，我们的数据揭示了Bcl 6在促进TFH细胞存活中的作用的新机制。
The transcriptional repressor Bcl6 controls development of the follicular helper T cell (TFH) lineage, however the precise mechanisms by which Bcl6 regulates this process are unclear. A model has been proposed whereby Bcl6 represses the differentiation of T cells into alternative effector lineages, thus favoring TFH differentiation. Analysis of T cell differentiation using Bcl6-deficient mice has been complicated by the strong pro-inflammatory phenotype of Bcl6-deficient myeloid cells. Here, we report data from a novel mouse model where Bcl6 is conditionally deleted in T cells (Bcl6fl/flCreCD4 mice). After immunization, PD-1high TFH cells in Bcl6fl/flCreCD4 mice are decreased over 90% compared to control mice, and antigen-specific IgG is sharply reduced. Residual PD-1high CXCR5+ TFH cells in Bcl6fl/flCreCD4 mice show a significantly higher rate of apoptosis than PD-1high CXCR5+ TFH cells in control mice. Immunization of Bcl6fl/flCreCD4 mice did not reveal enhanced differentiation into TH1, TH2 or TH17 lineages, although IL-10 expression by CD4 T cells was markedly elevated. Thus, T cell extrinsic factors appear to promote the increased TH1, TH2 and TH17 responses in germ-line Bcl6-deficient mice. Furthermore, IL-10 may be a key target gene for Bcl6 in CD4 T cells, which enables Bcl6 to promote the TFH cell phenotype. Finally, our data reveal a novel mechanism for the role of Bcl6 in promoting TFH cell survival.
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影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1126/science.1176676
发表时间：
2009-08-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Nurieva RI;Chung Y;Martinez GJ;Yang XO;Tanaka S;Matskevitch TD;Wang YH;Dong C
通讯作者：
Dong C
影响因子：
7
作者：
McHeyzer-Williams LJ;Pelletier N;Mark L;Fazilleau N;McHeyzer-Williams MG
通讯作者：
McHeyzer-Williams MG
影响因子：
4.4
作者：
Ohtsuka, Hiromi;Sakamoto, Akemi;Tokuhisa, Takeshi
通讯作者：
Tokuhisa, Takeshi
影响因子：
10.5
作者：
Barish, Grant D.;Yu, Ruth T.;Evans, Ronald M.
通讯作者：
Evans, Ronald M.