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Plasticity of TH17 cells in Peyer's patches is responsible for the induction of T cell–dependent IgA responses

Nature Immunology volume 14, pages 372379 (2013) | Download Citation

Abstract

Intestinal Peyer's patches are essential lymphoid organs for the generation of T cell–dependent immunoglobulin A (IgA) for gut homeostasis. Through the use of interleukin 17 (IL-17) fate-reporter mice, we found here that endogenous cells of the TH17 subset of helper T cells in lymphoid organs of naive mice 'preferentially' homed to the intestines and were maintained independently of IL-23. In Peyer's patches, such TH17 cells acquired a follicular helper T cell (TFH cell) phenotype and induced the development of IgA-producing germinal center B cells. Mice deficient in TH17 cells failed to generate antigen-specific IgA responses, which provides evidence that TH17 cells are the crucial subset required for the production of high-affinity T cell–dependent IgA.

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Acknowledgements

We thank D. Cua (Merck Research Laboratories) for the Il23a−/− mouse strain; A. Hayday (King's College London) for Tcra−/− mice; A. Zal and T. Zal (MD Anderson) for advice on microscopy of PP; the flow facility of the Medical Research Council National Institute for Medical Research for cell sorting; and Biological Services of the Medical Research Council National Institute for Medical Research for the breeding and maintenance of mouse strains. Supported by The European Mouse Mutant Archive, the European Union Framework Programme 7 Capacities Specific Program (for axenization), Medical Research Council UK (U117512792), Deutsche Forschungsgemeinschaft (TU 316/1-1 to. J.-E.T.) and Boehringer Ingelheim Fonds (M.V.).

Author information

Author notes

    • Keiji Hirota

    Present address: Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan.

    • Jan-Eric Turner
    •  & Matteo Villa

    These authors contributed equally to this work.

Affiliations

  1. Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, Mill Hill, London, UK.

    • Keiji Hirota
    • , Jan-Eric Turner
    • , Matteo Villa
    • , João H Duarte
    •  & Brigitta Stockinger
  2. Department of Lymphocyte Physiology, Instituto Gulbenkian De Ciência, Oeiras, Portugal.

    • Jocelyne Demengeot
  3. III Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Germany.

    • Oliver M Steinmetz

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Contributions

K.H. and B.S. conceived of the project, designed the experiments and wrote the paper; K.H. did most of the experiments; M.V., J-E.T. and J.H.D. did specific experiments; J.D. established the germ-free colony of reporter mice; and O.M.S. supplied bone marrow from Rorc−/− mice.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Brigitta Stockinger.

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DOI

https://doi.org/10.1038/ni.2552