Article abstract


Nature Immunology 8, 958 - 966 (2007)
Published online: 5 August 2007 | doi:10.1038/ni1500

The development of inflammatory TH-17 cells requires interferon-regulatory factor 4

Anne Brüstle1, Sylvia Heink2, Magdalena Huber1, Christine Rosenplänter1, Christine Stadelmann3, Philipp Yu4, Enrico Arpaia5, Tak W Mak5,6, Thomas Kamradt2 & Michael Lohoff1


Interferon-regulatory factor 4 (IRF4) is essential for the development of T helper type 2 cells. Here we show that IRF4 is also critical for the generation of interleukin 17–producing T helper cells (TH-17 cells), which are associated with experimental autoimmune encephalomyelitis. IRF4-deficient (Irf4-/-) mice did not develop experimental autoimmune encephalomyelitis, and T helper cells from such mice failed to differentiate into TH-17 cells. Transfer of wild-type T helper cells into Irf4-/- mice rendered the mice susceptible to experimental autoimmune encephalomyelitis. Irf4-/- T helper cells had less expression of RORgammat and more expression of Foxp3, transcription factors important for the differentiation of TH-17 and regulatory T cells, respectively. Altered regulation of both transcription factors contributed to the phenotype of Irf4-/- T helper cells. Our data position IRF4 at the center of T helper cell development, influencing not only T helper type 2 but also TH-17 differentiation.

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  1. Institut für Medizinische Mikrobiologie und Krankenhaushygiene, 35043 Marburg, Germany.
  2. Institut für Immunologie, Universitätsklinikum Jena, 07740 Jena, Germany.
  3. Institut für Neuropathologie, Universität Göttingen, 37075 Göttingen, Germany.
  4. Institut für Immunologie, 35043 Marburg, Germany.
  5. Advanced Medical Discovery Institute, University of Toronto, Toronto, Ontario, Canada M5G2C1.
  6. Departments of Immunology and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G2C1.

Correspondence to: Michael Lohoff1 e-mail: lohoff@med.uni-marburg.de


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