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Increased generation of Foxp3+ regulatory T cells by manipulating antigen presentation in the thymus

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  • Jiqiang Lin

    (Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    The Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine)

  • Lu Yang

    (Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    The Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine)

  • Hernandez Moura Silva

    (Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA)

  • Alissa Trzeciak

    (Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA)

  • Yongwon Choi

    (Institute for Immunology, University of Pennsylvania Perelman School of Medicine)

  • Susan R. Schwab

    (Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    New York University School of Medicine)

  • Michael L. Dustin

    (Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    New York University School of Medicine
    Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford)

  • Juan J. Lafaille

    (Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    New York University School of Medicine)

Abstract

Regulatory T-cell (Treg) selection in the thymus is essential to prevent autoimmune diseases. Although important rules for Treg selection have been established, there is controversy regarding the degree of self-reactivity displayed by T-cell receptors expressed by Treg cells. In this study we have developed a model of autoimmune skin inflammation, to determine key parameters in the generation of skin-reactive Treg cells in the thymus (tTreg). tTreg development is predominantly AIRE dependent, with an AIRE-independent component. Without the knowledge of antigen recognized by skin-reactive Treg cells, we are able to enhance skin-specific tTreg cell generation using three approaches. First, we increase medullary thymic epithelial cells by using mice lacking osteoprotegerin or by adding TRANCE (RANKL, Tnfsf11). Second, we inject intrathymically peripheral dendritic cells from skin-draining sites. Finally, we inject skin tissue lysates intrathymically. These findings have implications for enhancing the generation of organ-specific Treg cells in autoimmune diseases.

Suggested Citation

  • Jiqiang Lin & Lu Yang & Hernandez Moura Silva & Alissa Trzeciak & Yongwon Choi & Susan R. Schwab & Michael L. Dustin & Juan J. Lafaille, 2016. "Increased generation of Foxp3+ regulatory T cells by manipulating antigen presentation in the thymus," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10562
    DOI: 10.1038/ncomms10562
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