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, Tian Yu, Aoife M. McGinley, Shauna M. Quinn, Chandirasegaran Massilamany, N R Jayagopala Reddy, John V. Forrester, Kingston H.G. Mills

Research output: Contribution to journalArticle

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 (US)
Article numbere47121
JournalEMBO Reports
Volume20
Issue number5
DOIs
StatePublished - May 1 2019

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T-cells
Autoantigens
Regulatory T-Lymphocytes
Tretinoin
Autoimmunity
Immunization
Interleukin-2
Interleukin-17
Autoimmune Diseases
Interleukin-10
T-Lymphocytes
Th17 Cells
Th1 Cells
Autoimmune Experimental Encephalomyelitis
Uveitis
Antigens
Phenotype

Keywords

  • Th17 cell
  • autoimmune disease
  • immune suppression
  • regulatory T cell
  • retinoic acid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Raverdeau, M., Christofi, M., Malara, A., Wilk, M. M., Misiak, A., Kuffova, L., ... Mills, K. H. G. (2019). Retinoic acid-induced autoantigen-specific type 1 regulatory T cells suppress autoimmunity. EMBO Reports, 20(5), [e47121]. https://doi.org/10.15252/embr.201847121

Retinoic acid-induced autoantigen-specific type 1 regulatory T cells suppress autoimmunity. / Raverdeau, Mathilde; Christofi, Maria; Malara, Anna; Wilk, Mieszko M.; Misiak, Alicja; Kuffova, Lucia; Yu, Tian; McGinley, Aoife M.; Quinn, Shauna M.; Massilamany, Chandirasegaran; Reddy, N R Jayagopala; Forrester, John V.; Mills, Kingston H.G.

In: EMBO Reports, Vol. 20, No. 5, e47121, 01.05.2019.

Research output: Contribution to journalArticle

Raverdeau, M, Christofi, M, Malara, A, Wilk, MM, Misiak, A, Kuffova, L, Yu, T, McGinley, AM, Quinn, SM, Massilamany, C, Reddy, NRJ, Forrester, JV & Mills, KHG 2019, 'Retinoic acid-induced autoantigen-specific type 1 regulatory T cells suppress autoimmunity', EMBO Reports, vol. 20, no. 5, e47121. https://doi.org/10.15252/embr.201847121
Raverdeau M, Christofi M, Malara A, Wilk MM, Misiak A, Kuffova L et al. Retinoic acid-induced autoantigen-specific type 1 regulatory T cells suppress autoimmunity. EMBO Reports. 2019 May 1;20(5). e47121. https://doi.org/10.15252/embr.201847121
Raverdeau, Mathilde ; Christofi, Maria ; Malara, Anna ; Wilk, Mieszko M. ; Misiak, Alicja ; Kuffova, Lucia ; Yu, Tian ; McGinley, Aoife M. ; Quinn, Shauna M. ; Massilamany, Chandirasegaran ; Reddy, N R Jayagopala ; Forrester, John V. ; Mills, Kingston H.G. / Retinoic acid-induced autoantigen-specific type 1 regulatory T cells suppress autoimmunity. In: EMBO Reports. 2019 ; Vol. 20, No. 5.
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