生物
CD8型
下调和上调
转录因子
细胞生物学
细胞毒性T细胞
转化生长因子
T细胞
白细胞介素15
免疫学
细胞因子
免疫系统
白细胞介素
遗传学
基因
体外
作者
Laura K. Mackay,Erica Wynne-Jones,David Freestone,Daniel G. Pellicci,Lisa A. Mielke,Dane M. Newman,Asolina Braun,Frédérick Masson,Axel Kallies,Gabrielle T. Belz,Francis R. Carbone
出处
期刊:Immunity
[Elsevier]
日期:2015-12-01
卷期号:43 (6): 1101-1111
被引量:443
标识
DOI:10.1016/j.immuni.2015.11.008
摘要
Tissue-resident memory T (Trm) cells contribute to local immune protection in non-lymphoid tissues such as skin and mucosa, but little is known about their transcriptional regulation. Here we showed that CD8(+)CD103(+) Trm cells, independent of circulating memory T cells, were sufficient for protection against infection and described molecular elements that were crucial for their development in skin and lung. We demonstrated that the T-box transcription factors (TFs) Eomes and T-bet combined to control CD8(+)CD103(+) Trm cell formation, such that their coordinate downregulation was crucial for TGF-β cytokine signaling. TGF-β signaling, in turn, resulted in reciprocal T-box TF downregulation. However, whereas extinguishment of Eomes was necessary for CD8(+)CD103(+) Trm cell development, residual T-bet expression maintained cell surface interleukin-15 (IL-15) receptor β-chain (CD122) expression and thus IL-15 responsiveness. These findings indicate that the T-box TFs control the two cytokines, TGF-β and IL-15, which are pivotal for CD8(+)CD103(+) Trm cell development and survival.
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