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, Jay Reddy, John V. Forrester, Kingston H.G. Mills

Research output: Contribution to journalArticle

1 Citation (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 number5
DOIs
Publication statusPublished - 1 May 2019

Fingerprint

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

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
Raverdeau, Mathilde ; Christofi, Maria ; Malara, Anna ; Wilk, Mieszko M. ; Misiak, Alicja ; Kuffova, Lucia ; Yu, Tian ; McGinley, Aoife M. ; Quinn, Shauna M. ; Massilamany, Chandirasegaran ; Reddy, Jay ; 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.
@article{0565c78b62c24779902d81e7e7c10e8f,
title = "Retinoic acid-induced autoantigen-specific type 1 regulatory T cells suppress autoimmunity",
abstract = "Regulatory T (Treg) cells help to maintain tolerance and prevent the development of autoimmune diseases. Retinoic acid (RA) can promote peripheral conversion of na{\"i}ve 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.",
keywords = "autoimmune disease, immune suppression, regulatory T cell, retinoic acid, Th17 cell",
author = "Mathilde Raverdeau and Maria Christofi and Anna Malara and Wilk, {Mieszko M.} and Alicja Misiak and Lucia Kuffova and Tian Yu and McGinley, {Aoife M.} and Quinn, {Shauna M.} and Chandirasegaran Massilamany and Jay Reddy and Forrester, {John V.} and Mills, {Kingston H.G.}",
year = "2019",
month = "5",
day = "1",
doi = "10.15252/embr.201847121",
language = "English",
volume = "20",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "5",

}

Raverdeau, M, Christofi, M, Malara, A, Wilk, MM, Misiak, A, Kuffova, L, Yu, T, McGinley, AM, Quinn, SM, Massilamany, C, Reddy, J, 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

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, Jay; Forrester, John V.; Mills, Kingston H.G.

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

Research output: Contribution to journalArticle

TY - JOUR

T1 - Retinoic acid-induced autoantigen-specific type 1 regulatory T cells suppress autoimmunity

AU - Raverdeau, Mathilde

AU - Christofi, Maria

AU - Malara, Anna

AU - Wilk, Mieszko M.

AU - Misiak, Alicja

AU - Kuffova, Lucia

AU - Yu, Tian

AU - McGinley, Aoife M.

AU - Quinn, Shauna M.

AU - Massilamany, Chandirasegaran

AU - Reddy, Jay

AU - Forrester, John V.

AU - Mills, Kingston H.G.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - autoimmune disease

KW - immune suppression

KW - regulatory T cell

KW - retinoic acid

KW - Th17 cell

UR - http://www.scopus.com/inward/record.url?scp=85063146345&partnerID=8YFLogxK

U2 - 10.15252/embr.201847121

DO - 10.15252/embr.201847121

M3 - Article

VL - 20

JO - EMBO Reports

JF - EMBO Reports

SN - 1469-221X

IS - 5

M1 - e47121

ER -

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