Abstract
Senescent cells acquire a senescence-associated secretory phenotype (SASP), which is characterised by the increased production of pro-inflammatory factors.
Senescent CD4 T cells also exhibit the SASP and may contribute to a component of age-associated inflammatory responses called inflammaging. However, the mechanism behind the CD4 T-cell SASP remains unclear. We recently found that a T-cell–specific Menin deficiency results in the premature senescence of T cells after antigenic stimulation, which is accompanied by the SASP. Menin, in part, acts by targeting Bach2, which is known to regulate immune homeostasis. Menin binds to the Bach2 gene locus and controls its expression through the maintenance of active histone modification. Menin-dependent recruitment of PCAF and subsequent histone acetylation appears to be important for the maintenance of Bach2 expression. Menin binding at the Bach2 locus leads to a reduced Bach2 expression in the senescent CD4 T cells. The forced expression of Bach2 in menin-deficient CD4 T cells, as well as in senescent CD4 T cells, normalises the SASP. In addition, Bach2-deficient CD4 T cells exhibit SASP. These findings indicate that the Menin–Bach2 axis therefore plays a critical role in regulating the SASP in CD4 T cells.
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Yamashita, M., Kuwahara, M., Suzuki, J., Yamada, T. (2016). Controlling the Mechanism Underlying Chronic Inflammation Through the Epigenetic Modulation of CD4 T Cell Senescence. In: Miyasaka, M., Takatsu, K. (eds) Chronic Inflammation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56068-5_32
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DOI: https://doi.org/10.1007/978-4-431-56068-5_32
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