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.

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We thank S. Sakaguchi (Osaka University) for BALB/c Foxp3-IRES-Cre mice; B. Boldyreff (University of Southern Denmark) for Csnk2bfl mice on the C57BL/6 background; T. Sparwasser (TWINCORE) for C57BL/6 DEREG mice; K.A. Hogquist (University of Minnesota) for Nur77GFP mice; M. Lohoff (Philipps University Marburg) for C57BL/6 Irf4−/− mice; H.C. Probst (University Medical Center Mainz) for Ly5.1+ C57BL/6 mice; A. Waisman (University Medical Center Mainz) for CD90.1+ C57BL/6 mice; A. Nikolaev and S. Fischer for technical help, and D. O'Neill for critical reading of the manuscript. Supported by Deutsche Forschungsgemeinschaft (DFG BO 3306/1-1, SCHM 1014/7-1, SCHM 1014/5-1, SFB TR128 projects B4 (T.Bop. and F.Z.), A7 (A.W.) and A9 (H.J.), SFB 1066 projects B1 (E.S.) and B8 (T.Bop.), and BR 3754/2-1 (I.H. and M.B.)), International Graduate School of Immunotherapy (GRK 1043 project C4 (E.S. and T.Bop.)) and Forschungszentrum Immunologie of the University Medical Center of the Johannes Gutenberg-University Mainz (E.S. and T.Bop.).

Author information

Author notes

    • Edgar Schmitt
    •  & Tobias Bopp

    These authors jointly directed this work.


  1. Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

    • Alexander Ulges
    • , Matthias Klein
    • , Bastian Gerlitzki
    • , Markus Hoffmann
    • , Nadine Grebe
    • , Valérie Staudt
    • , Natascha Stergiou
    • , Toszka Bohn
    • , Till-Julius Brühl
    • , Sabine Muth
    • , Hajime Yurugi
    • , Krishnaraj Rajalingam
    • , Hans-Christian Probst
    • , Hansjörg Schild
    • , Edgar Schmitt
    •  & Tobias Bopp
  2. Department of Pulmonary Medicine, III. Medical Clinic of the University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.

    • Sebastian Reuter
  3. Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

    • Iris Bellinghausen
    • , Andrea Tuettenberg
    • , Susanne Hahn
    •  & Helmut Jonuleit
  4. Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

    • Sonja Reißig
    •  & Ari Waisman
  5. Department of Immunology and Virology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

    • Irma Haben
    •  & Minka Breloer
  6. Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

    • Frauke Zipp
  7. Experimentelle Stammzelltransplantation der Medizinische Klinik und Poliklinik II, Zentrum für Experimentelle Molekulare Medizin, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.

    • Andreas Beilhack
  8. INSERM, U823, Université Joseph Fourier-Grenoble1, Institut Albert Boniot, Faculté de Médecine, Domaine de la Merci, La Tronche, France.

    • Thierry Buchou
  9. INSERM U1036, Institute de Recherches en Technologies et Sciences pour le Vivant/Biologie du Cancer et de l'Infection, Commissariat à l'Énergie Atomique et aux Énerigies Alternatives Grenoble, Grenoble, France.

    • Odile Filhol-Cochet
  10. KinaseDetect, Aarslev, Denmark.

    • Brigitte Boldyreff


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A.U. performed and analyzed most experiments; M.K., B.G., M.H., N.G., V.S., N.S., T.Boh., T.-J.B., S.M., H.Y., K.R. and H.-C.P. helped design and perform some experiments; S.Reu. helped to perform and analyze mouse asthma experiments; M.K. conducted RNA-seq experiments; I.B., A.T., S.H., H.J. performed experiments involving human T cells; S.Rei. performed and analyzed adoptive transfer colitis experiments; I.H. and M.B. performed and analyzed nematode infection experiments; F.Z., A.W., A.B., T.Bu., O.F.-C., B.B. and H.S. helped design, analyze and interpret experiments; E.S. and T.Bop. supervised the project, designed experiments and wrote the manuscript; and all authors reviewed and approved the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Tobias Bopp.

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