Imperial College London
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Dr. Beth Holder

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer in Maternal and Fetal Health
 
 
 
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Contact

 

+44 (0)20 7594 1773b.holder Website

 
 
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Location

 

3 008Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Liberal:2015:10.1002/hep.27884,
author = {Liberal, R and Grant, CR and Holder, BS and Cardone, J and Martinez-Llordella, M and Ma, Y and Heneghan, MA and Mieli-Vergani, G and Vergani, D and Longhi, MS},
doi = {10.1002/hep.27884},
journal = {Hepatology},
pages = {863--875},
title = {In autoimmune hepatitis type 1 or the autoimmune hepatitis-sclerosing cholangitis variant defective regulatory T-cell responsiveness to IL-2 results in low IL-10 production and impaired suppression},
url = {http://dx.doi.org/10.1002/hep.27884},
volume = {62},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Defective immune regulation plays a permissive role enabling effector cells to initiate and perpetuate tissue damage, eventually resulting in autoimmune disease. Numerical and functional regulatory Tcell (Treg) impairment has been previously reported in autoimmune liver disease (AILD; including autoimmune hepatitis and autoimmune sclerosing cholangitis ASC). However, in these early reports, Tregs were phenotypically defined as CD4+CD25+ or CD4+CD25high cells. In the current study, we reexamined phenotypic and functional properties of Tregs by adopting a more refined definition of these cells that also includes negativity or low level of expression of CD127. We studied 43 AILD patients and 22 healthy subjects (HSs) and found that CD4+CD25+CD127− Tregs were decreased in the former. This decrease was more marked in patients with active disease than in those in remission. In AILD, Treg frequencies correlated inversely with parameters of disease activity and were not affected by immunosuppressive treatment. We also document, for the first time, that, in AILD, bonafide Tregs produce less interleukin (IL)−10 and are impaired in their ability to suppress CD4+CD25− target cell proliferation, a feature that in HSs, but not in AILDs, is dependent, at least in part, on IL10 secretion. Decreased IL10 production by Tregs in AILD is linked to poor responsiveness to IL2 and phospho signal transducer and activator of transcription 5 upregulation. Conclusion: Tregs are numerically impaired in AILD, this impairment being more prominent during active disease. Notably, defective IL10 production, resulting from low Treg responsiveness to IL2, contributes to Treg functional impairment. (Hepatology 2015;62:863–875)
AU  - Liberal,R
AU  - Grant,CR
AU  - Holder,BS
AU  - Cardone,J
AU  - Martinez-Llordella,M
AU  - Ma,Y
AU  - Heneghan,MA
AU  - Mieli-Vergani,G
AU  - Vergani,D
AU  - Longhi,MS
DO  - 10.1002/hep.27884
EP  - 875
PY  - 2015///
SN  - 0270-9139
SP  - 863
TI  - In autoimmune hepatitis type 1 or the autoimmune hepatitis-sclerosing cholangitis variant defective regulatory T-cell responsiveness to IL-2 results in low IL-10 production and impaired suppression
T2  - Hepatology
UR  - http://dx.doi.org/10.1002/hep.27884
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000360375100023&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.27884
VL  - 62
ER  -
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