Retinoic acid‐induced autoantigen‐specific type 1 regulatory T cells suppress autoimmunity

Mathilde Raverdeau, Maria Christofi, Anna Malara, Mieszko M Wilk, Alicja Misiak, Lucia Kuffova (Corresponding Author), Tian Yu, Aoife McGinley, Shauna M Quinn, Chandirasegaran Massilamany, Jay Reddy, John V Forrester, Kingston H. G. Mills

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2 Citations (Scopus)

Abstract

Regulatory T (Treg) cells help to maintain tolerance and prevent the development of autoimmune diseases. Retinoic acid (RA) can promote peripheral conversion of naïve T cells into Foxp3+ Treg cells. Here, we show that RA can act as an adjuvant to induce antigen‐specific type 1 Treg (Tr1) cells, which is augmented by co‐administration of IL‐2. Immunization of mice with the model antigen KLH in the presence of RA and IL‐2 induces T cells that secrete IL‐10, but not IL‐17 or IFN‐γ, and express LAG‐3, CD49b and PD‐1 but not Foxp3, a phenotype typical of Tr1 cells. Furthermore, immunization of mice with the autoantigen MOG in the presence of RA and IL‐2 induces Tr1 cells, which suppress pathogenic Th1 and Th17 cells that mediate the development of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease of the CNS. Furthermore, immunization with a surrogate autoantigen, RA and IL‐2 prevents development of spontaneous autoimmune uveitis. Our findings demonstrate that the induction of autoantigen‐specific Tr1 cells can prevent the development of autoimmunity.

Original languageEnglish
Article numbere47121
JournalEMBO reports
Volume20
Issue number3
Early online date20 Mar 2019
DOIs
Publication statusPublished - Mar 2019

Keywords

  • autoimmune disease
  • immune suppression
  • regulatory T cell
  • retinoic acid
  • Th17 cell
  • ACTIVATION
  • INSTABILITY
  • TOLERANCE
  • LOW-DOSE INTERLEUKIN-2
  • IL-2
  • INDUCTION
  • RESPONSES
  • THERAPY
  • GENERATION

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  • Cite this

    Raverdeau, M., Christofi, M., Malara, A., Wilk, M. M., Misiak, A., Kuffova, L., Yu, T., McGinley, A., Quinn, S. M., Massilamany, C., Reddy, J., Forrester, J. V., & Mills, K. H. G. (2019). Retinoic acid‐induced autoantigen‐specific type 1 regulatory T cells suppress autoimmunity. EMBO reports, 20(3), [e47121]. https://doi.org/10.15252/embr.201847121