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CD39 mediated regulation of Th17-cell effector function is impaired in juvenile autoimmune liver disease

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CD39 mediated regulation of Th17-cell effector function is impaired in juvenile autoimmune liver disease. / Liberal, Rodrigo ; Grant, Charlotte R.; Ma, Yun; Csizmadia, Eva; Jiang, Zhenghui Gordon; Heneghan, Michael A.; Yee, Eric U.; Mieli-Vergani, Giorgina; Vergani, Diego; Robson, Simon C.; Longhi, Maria Serena.

In: Journal of Autoimmunity, 20.05.2016.

Research output: Contribution to journalArticle

Harvard

Liberal, R, Grant, CR, Ma, Y, Csizmadia, E, Jiang, ZG, Heneghan, MA, Yee, EU, Mieli-Vergani, G, Vergani, D, Robson, SC & Longhi, MS 2016, 'CD39 mediated regulation of Th17-cell effector function is impaired in juvenile autoimmune liver disease', Journal of Autoimmunity. https://doi.org/10.1016/j.jaut.2016.05.005

APA

Liberal, R., Grant, C. R., Ma, Y., Csizmadia, E., Jiang, Z. G., Heneghan, M. A., ... Longhi, M. S. (2016). CD39 mediated regulation of Th17-cell effector function is impaired in juvenile autoimmune liver disease. Journal of Autoimmunity. https://doi.org/10.1016/j.jaut.2016.05.005

Vancouver

Liberal R, Grant CR, Ma Y, Csizmadia E, Jiang ZG, Heneghan MA et al. CD39 mediated regulation of Th17-cell effector function is impaired in juvenile autoimmune liver disease. Journal of Autoimmunity. 2016 May 20. https://doi.org/10.1016/j.jaut.2016.05.005

Author

Liberal, Rodrigo ; Grant, Charlotte R. ; Ma, Yun ; Csizmadia, Eva ; Jiang, Zhenghui Gordon ; Heneghan, Michael A. ; Yee, Eric U. ; Mieli-Vergani, Giorgina ; Vergani, Diego ; Robson, Simon C. ; Longhi, Maria Serena. / CD39 mediated regulation of Th17-cell effector function is impaired in juvenile autoimmune liver disease. In: Journal of Autoimmunity. 2016.

Bibtex Download

@article{0ccc850b44eb4b2a9bac7ba20f42b7ac,
title = "CD39 mediated regulation of Th17-cell effector function is impaired in juvenile autoimmune liver disease",
abstract = "Background & aims: T-helper-type 17 (Th17) cells are involved in autoimmune tissue damage. CD39 is an ectonucleotidase that catalyzes extracellular ATP/ADP hydrolysis, culminating in the generation of immunosuppressive adenosine. Functional CD39 expression confers immunosuppressive properties upon immune cells. As the proportion of CD39 lymphocytes is decreased in juvenile autoimmune liver disease (AILD), we have explored whether decreased CD39 expression is present on Th17 cells and whether this phenomenon is associated with heightened effector function and inflammation. Methods: Thirty-eight patients with juvenile AILD (22 autoimmune hepatitis and 16 autoimmune sclerosing cholangitis), 8 disease controls (DC) and 16 healthy subjects (HS) were studied. Peripheral blood cell phenotype was determined by flow cytometry; ability to suppress by inhibition of cell proliferation/ effector cytokine production; ectoenzymatic activity by thin layer chromatography; expression of adenosine receptor, adenosine deaminase (ADA) and phosphodiesterases (PDE) by quantitative real-time PCR or by Western Blot. Results: CD39{\th} Th17 (Th17CD39{\th}) cells from HS appear activated and contain high frequencies of lymphocytes producing regulatory cytokines. In AILD, however, Th17CD39{\th} cells are markedly diminished and fail to generate AMP/adenosine, thereby limiting control of both target cell proliferation and IL-17 production. When compared to HS, Th17 cells from AILD patients also show lower A2A adenosine receptor expression while displaying similar levels of PDE4A, PDE4B and ADA. Only rare Th17CD39{\th} cells are observed by liver immunohistochemistry. Conclusions: Th17CD39{\th} cells in juvenile AILD are both quantitatively decreased and qualitatively deficient. Low levels CD39 and A2A expression may contribute to the perpetuation of Th17 cell effector properties and unfettered inflammation in this disease.",
keywords = "Th17 cells, CD39, Adenosine, ATP, Autoimmune liver disease",
author = "Rodrigo Liberal and Grant, {Charlotte R.} and Yun Ma and Eva Csizmadia and Jiang, {Zhenghui Gordon} and Heneghan, {Michael A.} and Yee, {Eric U.} and Giorgina Mieli-Vergani and Diego Vergani and Robson, {Simon C.} and Longhi, {Maria Serena}",
year = "2016",
month = "5",
day = "20",
doi = "10.1016/j.jaut.2016.05.005",
language = "English",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "ACADEMIC PRESS INC",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - CD39 mediated regulation of Th17-cell effector function is impaired in juvenile autoimmune liver disease

AU - Liberal, Rodrigo

AU - Grant, Charlotte R.

AU - Ma, Yun

AU - Csizmadia, Eva

AU - Jiang, Zhenghui Gordon

AU - Heneghan, Michael A.

AU - Yee, Eric U.

AU - Mieli-Vergani, Giorgina

AU - Vergani, Diego

AU - Robson, Simon C.

AU - Longhi, Maria Serena

PY - 2016/5/20

Y1 - 2016/5/20

N2 - Background & aims: T-helper-type 17 (Th17) cells are involved in autoimmune tissue damage. CD39 is an ectonucleotidase that catalyzes extracellular ATP/ADP hydrolysis, culminating in the generation of immunosuppressive adenosine. Functional CD39 expression confers immunosuppressive properties upon immune cells. As the proportion of CD39 lymphocytes is decreased in juvenile autoimmune liver disease (AILD), we have explored whether decreased CD39 expression is present on Th17 cells and whether this phenomenon is associated with heightened effector function and inflammation. Methods: Thirty-eight patients with juvenile AILD (22 autoimmune hepatitis and 16 autoimmune sclerosing cholangitis), 8 disease controls (DC) and 16 healthy subjects (HS) were studied. Peripheral blood cell phenotype was determined by flow cytometry; ability to suppress by inhibition of cell proliferation/ effector cytokine production; ectoenzymatic activity by thin layer chromatography; expression of adenosine receptor, adenosine deaminase (ADA) and phosphodiesterases (PDE) by quantitative real-time PCR or by Western Blot. Results: CD39þ Th17 (Th17CD39þ) cells from HS appear activated and contain high frequencies of lymphocytes producing regulatory cytokines. In AILD, however, Th17CD39þ cells are markedly diminished and fail to generate AMP/adenosine, thereby limiting control of both target cell proliferation and IL-17 production. When compared to HS, Th17 cells from AILD patients also show lower A2A adenosine receptor expression while displaying similar levels of PDE4A, PDE4B and ADA. Only rare Th17CD39þ cells are observed by liver immunohistochemistry. Conclusions: Th17CD39þ cells in juvenile AILD are both quantitatively decreased and qualitatively deficient. Low levels CD39 and A2A expression may contribute to the perpetuation of Th17 cell effector properties and unfettered inflammation in this disease.

AB - Background & aims: T-helper-type 17 (Th17) cells are involved in autoimmune tissue damage. CD39 is an ectonucleotidase that catalyzes extracellular ATP/ADP hydrolysis, culminating in the generation of immunosuppressive adenosine. Functional CD39 expression confers immunosuppressive properties upon immune cells. As the proportion of CD39 lymphocytes is decreased in juvenile autoimmune liver disease (AILD), we have explored whether decreased CD39 expression is present on Th17 cells and whether this phenomenon is associated with heightened effector function and inflammation. Methods: Thirty-eight patients with juvenile AILD (22 autoimmune hepatitis and 16 autoimmune sclerosing cholangitis), 8 disease controls (DC) and 16 healthy subjects (HS) were studied. Peripheral blood cell phenotype was determined by flow cytometry; ability to suppress by inhibition of cell proliferation/ effector cytokine production; ectoenzymatic activity by thin layer chromatography; expression of adenosine receptor, adenosine deaminase (ADA) and phosphodiesterases (PDE) by quantitative real-time PCR or by Western Blot. Results: CD39þ Th17 (Th17CD39þ) cells from HS appear activated and contain high frequencies of lymphocytes producing regulatory cytokines. In AILD, however, Th17CD39þ cells are markedly diminished and fail to generate AMP/adenosine, thereby limiting control of both target cell proliferation and IL-17 production. When compared to HS, Th17 cells from AILD patients also show lower A2A adenosine receptor expression while displaying similar levels of PDE4A, PDE4B and ADA. Only rare Th17CD39þ cells are observed by liver immunohistochemistry. Conclusions: Th17CD39þ cells in juvenile AILD are both quantitatively decreased and qualitatively deficient. Low levels CD39 and A2A expression may contribute to the perpetuation of Th17 cell effector properties and unfettered inflammation in this disease.

KW - Th17 cells

KW - CD39

KW - Adenosine

KW - ATP

KW - Autoimmune liver disease

U2 - 10.1016/j.jaut.2016.05.005

DO - 10.1016/j.jaut.2016.05.005

M3 - Article

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

ER -

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