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Retinoic acid stabilizes antigen-specific regulatory T-cell function in autoimmune hepatitis type 2

Research output: Contribution to journalArticle

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Retinoic acid stabilizes antigen-specific regulatory T-cell function in autoimmune hepatitis type 2. / Holder, Beth S.; Grant, Charlotte R.; Gouveia Vasconcelos Rodrigues Liberal, Rodrigo Liberal; Ma, Yun; Heneghan, Michael A.; Mieli-Vergani, Giorgina; Vergani, Diego; Longhi, Maria Serena.

In: Journal of Autoimmunity, Vol. 53, No. C, 01.09.2014, p. 26-32.

Research output: Contribution to journalArticle

Harvard

Holder, BS, Grant, CR, Gouveia Vasconcelos Rodrigues Liberal, RL, Ma, Y, Heneghan, MA, Mieli-Vergani, G, Vergani, D & Longhi, MS 2014, 'Retinoic acid stabilizes antigen-specific regulatory T-cell function in autoimmune hepatitis type 2', Journal of Autoimmunity, vol. 53, no. C, pp. 26-32. https://doi.org/10.1016/j.jaut.2014.02.001

APA

Holder, B. S., Grant, C. R., Gouveia Vasconcelos Rodrigues Liberal, R. L., Ma, Y., Heneghan, M. A., Mieli-Vergani, G., Vergani, D., & Longhi, M. S. (2014). Retinoic acid stabilizes antigen-specific regulatory T-cell function in autoimmune hepatitis type 2. Journal of Autoimmunity, 53(C), 26-32. https://doi.org/10.1016/j.jaut.2014.02.001

Vancouver

Holder BS, Grant CR, Gouveia Vasconcelos Rodrigues Liberal RL, Ma Y, Heneghan MA, Mieli-Vergani G et al. Retinoic acid stabilizes antigen-specific regulatory T-cell function in autoimmune hepatitis type 2. Journal of Autoimmunity. 2014 Sep 1;53(C):26-32. https://doi.org/10.1016/j.jaut.2014.02.001

Author

Holder, Beth S. ; Grant, Charlotte R. ; Gouveia Vasconcelos Rodrigues Liberal, Rodrigo Liberal ; Ma, Yun ; Heneghan, Michael A. ; Mieli-Vergani, Giorgina ; Vergani, Diego ; Longhi, Maria Serena. / Retinoic acid stabilizes antigen-specific regulatory T-cell function in autoimmune hepatitis type 2. In: Journal of Autoimmunity. 2014 ; Vol. 53, No. C. pp. 26-32.

Bibtex Download

@article{8313c76de1ce4f429e176e6ec30fa869,
title = "Retinoic acid stabilizes antigen-specific regulatory T-cell function in autoimmune hepatitis type 2",
abstract = "Imbalance between effector and regulatory T-cells (Treg) underlies the loss of immune-tolerance to self-antigens in autoimmune disease. In autoimmune hepatitis type 2 (AIH-2), effector CD4 T-cell immune responses to cytochrome P450IID6 (CYP2D6) are permitted by numerically and functionally impaired Treg. Restoration of CYP2D6-specific Treg in AIH-2 would enable control over effectors sharing the same antigen specificity, leading to re-establishment of immune-tolerance. We have previously developed a protocol for generating antigen-specific Treg through co-culture with semi-mature dendritic cells presenting CYP2D6 peptides. In this study, we aimed to explore phenotypic and functional features of patient Treg compared to health, to test Treg stability under pro-inflammatory conditions, and to investigate the potential benefit of supplementation with all-trans-retinoic acid (RA) or rapamycin (RP), agents proven to enhance Treg function.We show that antigen-specific Treg from patients have comparable phenotypic and functional features to those from healthy controls, suppressing both proliferation and pro-inflammatory cytokine production by effector cells. Treg exposure to inflammatory challenge results in decreased suppressive function and up-regulation of Th1/Th2/Th17 transcription factors both in health and AIH-2. The increase of Th1 and Th17 transcription factors is limited by addition of RA in controls and Th1 expression is decreased by RP in patients. Importantly, inflammation-induced decrease in Treg function is also abrogated by RA/RP in health and RA in patients.Our data provide important information for the optimization of protocols aiming at generating antigen-specific Treg for treatment of autoimmune disease and for understanding their biology upon pro-inflammatory challenge and RP/RA supplementation.",
keywords = "Autoimmune liver disease, Liver autoantigen, Regulatory T-cell immunotherapy, Stability, Tolerance",
author = "Holder, {Beth S.} and Grant, {Charlotte R.} and {Gouveia Vasconcelos Rodrigues Liberal}, {Rodrigo Liberal} and Yun Ma and Heneghan, {Michael A.} and Giorgina Mieli-Vergani and Diego Vergani and Longhi, {Maria Serena}",
year = "2014",
month = sep,
day = "1",
doi = "10.1016/j.jaut.2014.02.001",
language = "English",
volume = "53",
pages = "26--32",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "ACADEMIC PRESS INC",
number = "C",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Retinoic acid stabilizes antigen-specific regulatory T-cell function in autoimmune hepatitis type 2

AU - Holder, Beth S.

AU - Grant, Charlotte R.

AU - Gouveia Vasconcelos Rodrigues Liberal, Rodrigo Liberal

AU - Ma, Yun

AU - Heneghan, Michael A.

AU - Mieli-Vergani, Giorgina

AU - Vergani, Diego

AU - Longhi, Maria Serena

PY - 2014/9/1

Y1 - 2014/9/1

N2 - Imbalance between effector and regulatory T-cells (Treg) underlies the loss of immune-tolerance to self-antigens in autoimmune disease. In autoimmune hepatitis type 2 (AIH-2), effector CD4 T-cell immune responses to cytochrome P450IID6 (CYP2D6) are permitted by numerically and functionally impaired Treg. Restoration of CYP2D6-specific Treg in AIH-2 would enable control over effectors sharing the same antigen specificity, leading to re-establishment of immune-tolerance. We have previously developed a protocol for generating antigen-specific Treg through co-culture with semi-mature dendritic cells presenting CYP2D6 peptides. In this study, we aimed to explore phenotypic and functional features of patient Treg compared to health, to test Treg stability under pro-inflammatory conditions, and to investigate the potential benefit of supplementation with all-trans-retinoic acid (RA) or rapamycin (RP), agents proven to enhance Treg function.We show that antigen-specific Treg from patients have comparable phenotypic and functional features to those from healthy controls, suppressing both proliferation and pro-inflammatory cytokine production by effector cells. Treg exposure to inflammatory challenge results in decreased suppressive function and up-regulation of Th1/Th2/Th17 transcription factors both in health and AIH-2. The increase of Th1 and Th17 transcription factors is limited by addition of RA in controls and Th1 expression is decreased by RP in patients. Importantly, inflammation-induced decrease in Treg function is also abrogated by RA/RP in health and RA in patients.Our data provide important information for the optimization of protocols aiming at generating antigen-specific Treg for treatment of autoimmune disease and for understanding their biology upon pro-inflammatory challenge and RP/RA supplementation.

AB - Imbalance between effector and regulatory T-cells (Treg) underlies the loss of immune-tolerance to self-antigens in autoimmune disease. In autoimmune hepatitis type 2 (AIH-2), effector CD4 T-cell immune responses to cytochrome P450IID6 (CYP2D6) are permitted by numerically and functionally impaired Treg. Restoration of CYP2D6-specific Treg in AIH-2 would enable control over effectors sharing the same antigen specificity, leading to re-establishment of immune-tolerance. We have previously developed a protocol for generating antigen-specific Treg through co-culture with semi-mature dendritic cells presenting CYP2D6 peptides. In this study, we aimed to explore phenotypic and functional features of patient Treg compared to health, to test Treg stability under pro-inflammatory conditions, and to investigate the potential benefit of supplementation with all-trans-retinoic acid (RA) or rapamycin (RP), agents proven to enhance Treg function.We show that antigen-specific Treg from patients have comparable phenotypic and functional features to those from healthy controls, suppressing both proliferation and pro-inflammatory cytokine production by effector cells. Treg exposure to inflammatory challenge results in decreased suppressive function and up-regulation of Th1/Th2/Th17 transcription factors both in health and AIH-2. The increase of Th1 and Th17 transcription factors is limited by addition of RA in controls and Th1 expression is decreased by RP in patients. Importantly, inflammation-induced decrease in Treg function is also abrogated by RA/RP in health and RA in patients.Our data provide important information for the optimization of protocols aiming at generating antigen-specific Treg for treatment of autoimmune disease and for understanding their biology upon pro-inflammatory challenge and RP/RA supplementation.

KW - Autoimmune liver disease

KW - Liver autoantigen

KW - Regulatory T-cell immunotherapy

KW - Stability

KW - Tolerance

UR - http://www.scopus.com/inward/record.url?scp=84926407089&partnerID=8YFLogxK

U2 - 10.1016/j.jaut.2014.02.001

DO - 10.1016/j.jaut.2014.02.001

M3 - Article

AN - SCOPUS:84926407089

VL - 53

SP - 26

EP - 32

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

IS - C

ER -

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