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Th17 cells, pathogenic or not? TGF-β3 imposes the embargo

Cellular & Molecular Immunology volume 10, pages 101–102 (2013)Cite this article

Th17 cells that express lineage-specific transcription factor RORC in human (and RORγt in mice) and produce cytokines IL-17A, IL-17F, IL-21, GM-CSF and IL-22, constitute distinct subset of CD4+ T cells.1 Various reports indicated that Th17 cells have a critical role in the pathogenesis of several inflammatory and autoimmune diseases including rheumatoid arthritis, multiple sclerosis and psoriasis.2 However, all IL-17-producing Th17 cells are not pathogenic. For example, existence of regulatory Th17 cells with immune-suppressive phenotype had been detected in small intestine.3 As such, the factor(s) that govern(s) programming of non-pathogenic versus pathogenic Th17 cells is not completely known. Combination of TGF-β1 and IL-6 is sufficient to induce Th17 differentiation from naïve CD4+ T cells, but IL-23 produced by the activated innate cells is critical for stabilizing Th17 cells and for acquiring pathogenic functions.1,4 Also results from experimental autoimmune encephalomyelitis (EAE) in T-bet-deficient mice demonstrated that encephalitogenic Th17 cells express Th1-transcription factor T-bet and encephalitogenecity of both Th1 and Th17 cells is governed by T-bet and not by T-cell lineage-specific cytokines IFN-γ and IL-17.5 Therefore, in a recent article in Nature mmunology,6 Vijay Kuchroo and his colleagues aimed at identifying the IL-23-dependent effector molecule that imparts pathogenic phenotype to Th17 cells and the role of T-bet in the process.

By using EAE model, the authors first reconfirmed the role of IL-23 in the induction of pathogenic Th17 cells. Adoptive transfer of TGF-β1, IL-6 and IL-23-differentiated MOG-specific CD4+ T cells led to development of severe disease in mice, whereas mild or no disease was observed when TGF-β1 and IL-6-differentiated T cells were transferred. Analysis of molecular changes in IL-23-exposed Th17 cell revealed considerable induction of TGF-β3 and provided the clue for the role of TGF-β3 in the induction of pathogenic Th17 cells.

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Acknowledgements

This work is supported by Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie, Université Paris Descartes and European Community's Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No: 260338 ALLFUN and ANR-10-BLAN-1309 HYDROPHOBIN.

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  1. Unité 872, Institut National de la Santé et de la Recherche Médicale, Paris, France,

    Meenu Sharma, Srini V Kaveri & Jagadeesh Bayry

  2. Université de Technologie de Compiègne, Compiègne, France

    Meenu Sharma

  3. Centre de Recherche des Cordeliers, Equipe 16- Immunopathology and therapeutic immunointervention, Université Pierre et Marie Curie, Paris, France

    Srini V Kaveri & Jagadeesh Bayry

  4. Université Paris Descartes, Paris, France,

    Srini V Kaveri & Jagadeesh Bayry

  5. International Associated Laboratory IMPACT (Institut National de la Santé et de la Recherche Médicale, France—Indian Council of Medical Research, India), National Institute of Immunohaematology, Mumbai, India

    Srini V Kaveri & Jagadeesh Bayry

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  1. Meenu Sharma
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Correspondence to Jagadeesh Bayry.

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Sharma, M., Kaveri, S. & Bayry, J. Th17 cells, pathogenic or not? TGF-β3 imposes the embargo. Cell Mol Immunol 10, 101–102 (2013). https://doi.org/10.1038/cmi.2012.72

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