Protein kinase CK2 enables regulatory T cells to suppress excessive TH2 responses in vivo

• Published in: Nature immunology Vol. 16; no. 3; pp. 267 - 275
• Main Authors: Ulges, Alexander, Klein, Matthias, Reuter, Sebastian, Gerlitzki, Bastian, Hoffmann, Markus, Grebe, Nadine, Staudt, Valérie, Stergiou, Natascha, Bohn, Toszka, Brühl, Till-Julius, Muth, Sabine, Yurugi, Hajime, Rajalingam, Krishnaraj, Bellinghausen, Iris, Tuettenberg, Andrea, Hahn, Susanne, Reißig, Sonja, Haben, Irma, Zipp, Frauke, Waisman, Ari, Probst, Hans-Christian, Beilhack, Andreas, Buchou, Thierry, Filhol-Cochet, Odile, Boldyreff, Brigitte, Breloer, Minka, Jonuleit, Helmut, Schild, Hansjörg, Schmitt, Edgar, Bopp, Tobias
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2015; Nature Publishing Group
• Subjects: 13; 13/31; 38; 38/91; 631/250/2152/569/2495; 64; 64/110; 82; 96; Animals; Biomedicine; Casein Kinase II - immunology; CD4-Positive T-Lymphocytes - enzymology; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation - immunology; Cell Growth Processes - immunology; Cell Line; Dendritic Cells - enzymology; Dendritic Cells - immunology; Forkhead Transcription Factors - immunology; Humans; Hypersensitivity - blood; Hypersensitivity - immunology; Immune response; Immunology; Infectious Diseases; Interferon Regulatory Factors - immunology; Leukocytes, Mononuclear - immunology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Receptors, Cell Surface - immunology; T-Lymphocytes, Regulatory - enzymology; T-Lymphocytes, Regulatory - immunology; Th2 Cells - enzymology; Th2 Cells - immunology
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.3083

The mechanisms that control the suppressive function of T reg cells in specific tissues are unclear. Bopp and colleagues show that T reg cells have high expression of kinase CK2 and this is critical for their ability to suppress type 2 responses in the lungs. 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 (T reg cells). However, how a tissue- and cell type–specific suppressor program of T reg cells is mechanistically orchestrated has remained largely unexplored. Through the use of T reg cell–specific gene targeting, we found that the suppression of allergic immune responses in the lungs mediated by T helper type 2 (T H 2) cells was dependent on the activity of the protein kinase CK2. Genetic ablation of the β-subunit of CK2 specifically in T reg cells resulted in the proliferation of a hitherto-unexplored ILT3 + T reg cell subpopulation that was unable to control the maturation of IRF4 + PD-L2 + dendritic cells required for the development of T H 2 responses in vivo .