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The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells

Nature Immunology volume 10, pages 167–175 (2009)Cite this article

Abstract

The inducible costimulatory molecule ICOS has been suggested to be important in the development of interleukin 17 (IL-17)-producing helper T cells (TH-17 cells) and of follicular helper T cells (TFH cells). Here we show that ICOS-deficient mice had no defect in TH-17 differentiation but had fewer TH-17 cells after IL-23 stimulation and fewer TFH cells. We also show that TFH cells produced IL-17 and that TFH cells in ICOS-deficient mice were defective in IL-17 production. Both TH-17 and TFH cells had higher expression of the transcription factor c-Maf. Genetic loss of c-Maf resulted in a defect in IL-21 production and fewer TH-17 and TFH cells. Thus our data suggest that ICOS-induced c-Maf regulates IL-21 production that in turn regulates the expansion of TH-17 and TFH cells.

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Figure 1: ICOS is not crucial for TH-17 differentiation in vitro.
Figure 2: ICOS is not crucial for TH-17 differentiation in vivo or for the induction of acute EAE.
Figure 3: TFH cells produce IL-17.
Figure 4: ICOS-deficient TFH cells are defective in IL-17 production.
Figure 5: ICOS-deficient T cells have a defect in secondary TH-17 responses.
Figure 6: The function of c-Maf in TH-17 differentiation.

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Acknowledgements

We thank D. Kozoriz for cell sorting, and A. Jaeger, S. Liu and L. Francisco for comments. A.H.S. and V.K.K. are joint senior authors. Supported by the National Institutes of Health (1R01NS045937-01, 2R01NS35685-06, 2R37NS30843-11, 1R01A144880-03, P01NS38037-04 and 1R01NS046414 to V.K.K.; 2P01A139671-07 and 1P01AI56299 to V.K.K. and A.H.S.; R37 AI38310 to A.H.S.; Javits Neuroscience Investigator Award to V.K.K.), the National Multiple Sclerosis Society (RG-2571-D-9), the European Commission (A.T.B.) and the Deutsche Forschungsgemeinschaft (M.M.).

Author information

Author notes

  1. Hulin Jin and Alison M Paterson: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.,

    Aurelie T Bauquet, Hulin Jin, Meike Mitsdoerffer & Vijay K Kuchroo

  2. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Alison M Paterson & Arlene H Sharpe

  3. Division of Rheumatology, Immunology and Allergy and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA

    I-Cheng Ho

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Contributions

A.T.B. and A.M.P. designed experiments, did experiments, collected data and contributed to the writing of the manuscript. H.J. undertook expression profiling of TH-17 cells and analyzed c-Maf expression in different cell types. M.M. provided help in performing experiments. A.H.S. and V.K.K. supervised the project and edited the manuscript. I.-C.H. provided c-Maf–deficient mice.

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Correspondence to Vijay K Kuchroo.

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Bauquet, A., Jin, H., Paterson, A. et al. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nat Immunol 10, 167–175 (2009). https://doi.org/10.1038/ni.1690

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