The Menin-Bach2 axis is critical for regulating CD4 T-cell senescence and cytokine homeostasis.
The Menin-Bach2 axis is critical for regulating CD4 T-cell senescence and cytokine homeostasis.
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DOI：
10.1038/ncomms4555
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发表时间：
2014-04-02
影响因子：
16.6
通讯作者：
Yamashita, Masakatsu
中科院分区：
文献类型：
--
作者：
Kuwahara, Makoto;Suzuki, Junpei;Tofukuji, Soichi;Yamada, Takeshi;Kanoh, Makoto;Matsumoto, Akira;Maruyama, Saho;Kometani, Kohei;Kurosaki, Tomohiro;Ohara, Osamu;Nakayama, Toshinori;Yamashita, Masakatsu
虽然CD4T细胞衰老在免疫衰老中起着重要作用，但这一过程背后的机制尚不清楚。在这里，我们发现T细胞特异性的Menin缺乏导致了CD4T细胞的提前衰老，在抗原刺激和细胞因子产生失调后伴随着衰老相关的分泌表型。梅宁是体内抗原刺激的CD4T细胞扩增和存活所必需的，它通过靶向Bach2发挥作用，已知Bach2调节免疫稳态和细胞因子的产生。Menin与Bach2基因结合，通过维持组蛋白乙酰化来控制其表达。在衰老的CD4T细胞中，Bach2基因的Menin结合和Bach2的表达减少。这些发现揭示了Menin-Bach2途径在调节CD4T细胞衰老和细胞因子稳态中的重要作用，从而表明该途径参与了免疫衰老的抑制。免疫衰老尤其影响T细胞室，并与年龄相关的免疫功能下降有关。在这里，作者表明，肿瘤抑制因子Menin的缺失导致了CD4T细胞的过早衰老。
Although CD4 T-cell senescence plays an important role in immunosenescence, the mechanism behind this process remains unclear. Here we show that T cell-specific Menin deficiency results in the premature senescence of CD4 T cells, which is accompanied by the senescence-associated secretory phenotype after antigenic stimulation and dysregulated cytokine production. Menin is required for the expansion and survival of antigen-stimulated CD4 T cells in vivo and acts by targeting Bach2, which is known to regulate immune homeostasis and cytokine production. Menin binds to the Bach2 locus and controls its expression through maintenance of histone acetylation. Menin binding at the Bach2 locus and the Bach2 expression are decreased in the senescent CD4 T cells. These findings reveal a critical role of the Menin-Bach2 pathway in regulating CD4 T-cell senescence and cytokine homeostasis, thus indicating the involvement of this pathway in the inhibition of immunosenescence. Immunosenescence particularly affects the T-cell compartment and is involved in the age-related decline of immune functions. Here, the authors show that the absence of the tumour suppressor Menin results in premature senescence of CD4 T cells.
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影响因子：
13.6
作者：
Freund A;Orjalo AV;Desprez PY;Campisi J
通讯作者：
Campisi J
影响因子：
16.8
作者：
Dohi, Yoshihiro;Ikura, Tsuyoshi;Igarashi, Kazuhiko
通讯作者：
Igarashi, Kazuhiko
影响因子：
16
作者：
Hughes, CM;Rozenblatt-Rosen, O;Meyerson, M
通讯作者：
Meyerson, M
影响因子：
10.5
作者：
Chien, Yuchen;Scuoppo, Claudio;Lowe, Scott W.
通讯作者：
Lowe, Scott W.
影响因子：
4.1
作者：
Balogh, Katalin;Patocs, Attila;Racz, Karoly
通讯作者：
Racz, Karoly