Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Department of Pulmonary Medicine, III. Medical Clinic of the University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.
Nat Immunol. 2015 Mar;16(3):267-75. doi: 10.1038/ni.3083. Epub 2015 Jan 19.
The quality of the adaptive immune response depends on the differentiation of distinct CD4(+) helper T cell subsets, and the magnitude of an immune response is controlled by CD4(+)Foxp3(+) regulatory T cells (Treg cells). However, how a tissue- and cell type-specific suppressor program of Treg cells is mechanistically orchestrated has remained largely unexplored. Through the use of Treg cell-specific gene targeting, we found that the suppression of allergic immune responses in the lungs mediated by T helper type 2 (TH2) cells was dependent on the activity of the protein kinase CK2. Genetic ablation of the β-subunit of CK2 specifically in Treg cells resulted in the proliferation of a hitherto-unexplored ILT3(+) Treg cell subpopulation that was unable to control the maturation of IRF4(+)PD-L2(+) dendritic cells required for the development of TH2 responses in vivo.
适应性免疫反应的质量取决于不同的 CD4(+)辅助性 T 细胞亚群的分化，而免疫反应的强度则由 CD4(+)Foxp3(+)调节性 T 细胞（Treg 细胞）控制。然而，Treg 细胞的组织和细胞类型特异性抑制程序是如何在机制上协调的，在很大程度上仍未得到探索。通过使用 Treg 细胞特异性基因靶向，我们发现，TH2 细胞介导的肺部过敏免疫反应的抑制依赖于蛋白激酶 CK2 的活性。CK2 的β亚单位在 Treg 细胞中的特异性基因缺失导致了一个迄今为止尚未被探索的 ILT3(+)Treg 细胞亚群的增殖，该亚群无法控制体内 TH2 反应所需的 IRF4(+)PD-L2(+)树突状细胞的成熟。
