The timing of differentiation and potency of CD8 effector function is set by RNA binding proteins.
The timing of differentiation and potency of CD8 effector function is set by RNA binding proteins.
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DOI：
10.1038/s41467-022-29979-x
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发表时间：
2022-04-27
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
CD 8 + T细胞分化为效应细胞在抗原遇到后早期通过来自T细胞抗原受体和共刺激分子的信号启动。然而，建立分化的时间和速率的分子机制尚未确定。在这里，我们表明RNA结合蛋白（RBP）ZFP 36和ZFP 36 L1限制了活化的幼稚CD 8 + T细胞的分化率和产生的细胞毒性淋巴细胞的效力。RBP在早期和短时间窗内发挥作用，通过直接结合NF-κB、Irf 8和Notch 1转录因子和细胞因子（包括IL 2）的mRNA，增强对CD 28共刺激的依赖性，以实现完全T细胞活化和效应分化。它们在T细胞中的缺失，或少量缺乏RBP的CD 8 + T细胞的过继转移，促进了对甲型流感病毒感染的恢复力，而没有免疫病理学。这些发现强调了ZFP 36和ZFP 36 L1作为早期T细胞活化信号整合的节点，控制CD 8 + T细胞应答的速度和质量。RNA结合蛋白（RBP）在T细胞活化和分化中具有功能。在这里，作者表明，在不存在两种RBP，ZFP 36和ZFP 36 L1的情况下，T细胞更快地获得上级效应子能力，显示出RBP在T细胞活化和分化中的限制性功能。
CD8+ T cell differentiation into effector cells is initiated early after antigen encounter by signals from the T cell antigen receptor and costimulatory molecules. The molecular mechanisms that establish the timing and rate of differentiation however are not defined. Here we show that the RNA binding proteins (RBP) ZFP36 and ZFP36L1 limit the rate of differentiation of activated naïve CD8+ T cells and the potency of the resulting cytotoxic lymphocytes. The RBP function in an early and short temporal window to enforce dependency on costimulation via CD28 for full T cell activation and effector differentiation by directly binding mRNA of NF-κB, Irf8 and Notch1 transcription factors and cytokines, including Il2. Their absence in T cells, or the adoptive transfer of small numbers of CD8+ T cells lacking the RBP, promotes resilience to influenza A virus infection without immunopathology. These findings highlight ZFP36 and ZFP36L1 as nodes for the integration of the early T cell activation signals controlling the speed and quality of the CD8+ T cell response. RNA binding proteins (RBP) have a function in T cell activation and differentiation. Here the authors show that in the absence of two RBPs, ZFP36 and ZFP36L1, T cells acquire more rapidly superior effector capabilities, showing a limiting function for RBP in T cell activation and differentiation.
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CD28在T细胞稳态中共同刺激：最近的观点。
影响因子：
7.2
作者：
Beyersdorf N;Kerkau T;Hünig T
通讯作者：
Hünig T
影响因子：
5.6
作者：
Bennett TJ;Udupa VAV;Turner SJ
通讯作者：
Turner SJ
影响因子：
20.3
作者：
Chiu, Christopher;Heaps, Adrian G.;Callan, Margaret F. C.
通讯作者：
Callan, Margaret F. C.
影响因子：
4.4
作者：
Matsumoto, M;Yamada, T;Mitani, T
通讯作者：
Mitani, T
DOI：
10.4049/jimmunol.0802598
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cho OH;Shin HM;Miele L;Golde TE;Fauq A;Minter LM;Osborne BA
通讯作者：
Osborne BA