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Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation.

Christakoudi, S; Runglall, M; Mobillo, P; Rebollo-Mesa, I; Tsui, T-L; Nova-Lamperti, E; Norris, S; Kamra, Y; Hilton, R; Bhandari, S; et al. Christakoudi, S; Runglall, M; Mobillo, P; Rebollo-Mesa, I; Tsui, T-L; Nova-Lamperti, E; Norris, S; Kamra, Y; Hilton, R; Bhandari, S; Baker, R; Berglund, D; Carr, S; Game, D; Griffin, S; Kalra, PA; Lewis, R; Mark, PB; Marks, SD; Macphee, I; McKane, W; Mohaupt, MG; Pararajasingam, R; Kon, SP; Serón, D; Sinha, M; Tucker, B; Viklický, O; Lechler, RI; Lord, GM; Stahl, D; Hernandez-Fuentes, MP (2018) Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation. Mol Cell Endocrinol, 473. pp. 205-216. ISSN 1872-8057 https://doi.org/10.1016/j.mce.2018.01.021
SGUL Authors: MacPhee, Iain Angus MacGregor

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Abstract

Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared. Healthy controls (n = 14) were used as reference. The anti-inflammatory glucocorticoid receptor (NR3C1) and the cortisol-activating HSD11B1 and H6PD genes were up-regulated in CR and were lowest in tolerant patients. The pro-inflammatory mineralocorticoid gene (NR3C2) was downregulated in stable and CR patients. NR3C1 was associated with neutrophils and NR3C2 with T-cells. Steroid conversion and receptor genes, alone, enabled classification of tolerant patients and were major contributors to gene-expression signatures of both, tolerance and CR, alongside known tolerance-associated genes, revealing a key role of steroid regulation and response in kidney transplantation.

Item Type: Article
Additional Information: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Chronic rejection, Kidney, Steroid conversion, Steroid receptor genes, Tolerance, Transplantation, Chronic rejection, Kidney, Steroid conversion, Steroid receptor genes, Tolerance, Transplantation, 06 Biological Sciences, 11 Medical And Health Sciences, 07 Agricultural And Veterinary Sciences
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Journal or Publication Title: Mol Cell Endocrinol
ISSN: 1872-8057
Language: eng
Dates:
DateEvent
15 September 2018Published
7 February 2018Published Online
29 January 2018Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
305147: BIO-DrIMSeventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
G0801537/ID: 88245Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/J006742/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
R080530Guy's and St Thomas' Charityhttp://dx.doi.org/10.13039/501100000380
R090782Guy's and St Thomas' Charityhttp://dx.doi.org/10.13039/501100000380
HEALTH-F5–2010–260687Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
PubMed ID: 29427591
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109681
Publisher's version: https://doi.org/10.1016/j.mce.2018.01.021

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