Programming of Distinct Chemokine-Dependent and -Independent Search Strategies for Th1 and Th2 Cells Optimizes Function at Inflamed Sites
Programming of Distinct Chemokine-Dependent and -Independent Search Strategies for Th1 and Th2 Cells Optimizes Function at Inflamed Sites
复制标题
DOI：
10.1016/j.immuni.2019.06.026
复制
发表时间：
2019-08-20
期刊：
影响因子：
32.4
通讯作者：
Fowell, Deborah J.
中科院分区：
文献类型：
--
作者：
Gaylo-Moynihan, Alison;Prizant, Hen;Fowell, Deborah J.
辅助T细胞（Th）分化驱动特定的基因程序，在感染部位指示效应T细胞的功能。在这里，我们已经证明了Th细胞分化也施加了离散的运动基因程序，这些程序塑造了发炎真皮中Th1和Th2细胞的导航。Th1细胞以G蛋白偶联受体（GPCR）和趋化因子依赖的方式扫描较小的组织区域，而Th2细胞以不依赖GPCR信号的方式扫描较大的组织区域。间质迁移的差异趋化因子依赖与STAT6转录因子依赖性整合素α (v) β(3)表达的编程有关：Th2细胞分化导致相对于Th1细胞的高α (v) β(3)表达。Th1和Th2细胞的运动模式可以简单地通过控制细胞表面α (v) β(3)的数量来切换。偏离分化过程中建立的运动模式会损害效应者的功能。因此，α (v) β(3)的程序化表达调节了效应T细胞对环境线索的依赖，以最佳地探索炎症组织。
T-helper (Th) cell differentiation drives specialized gene programs that dictate effector T cell function at sites of infection. Here, we have shown Th cell differentiation also imposes discrete motility gene programs that shape Th1 and Th2 cell navigation of the inflamed dermis. Th1 cells scanned a smaller tissue area in a G protein-coupled receptor (GPCR) and chemokine-dependent fashion, while Th2 cells scanned a larger tissue area independent of GPCR signals. Differential chemokine reliance for interstitial migration was linked to STAT6 transcription-factor-dependent programming of integrin alpha(v)beta(3) expression: Th2 cell differentiation led to high alpha(v)beta(3) expression relative to Th1 cells. Th1 and Th2 cell modes of motility could be switched simply by manipulating the amount of alpha(v)beta(3) on the cell surface. Deviating motility modes from those established during differentiation impaired effector function. Thus, programmed expression of alpha(v)beta(3) tunes effector T cell reliance on environmental cues for optimal exploration of inflamed tissues.