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

被引:9
|
作者
Christakoudi, Sofia [1 ,2 ]
Runglall, Manohursingh [3 ,4 ]
Mobillo, Paula [1 ]
Rebollo-Mesa, Irene [1 ,2 ,24 ]
Tsui, Tjir-Li [1 ,5 ]
Nova-Lamperti, Estefania [1 ,25 ]
Norris, Sonia [1 ,26 ]
Kamra, Yogesh [1 ,27 ]
Hilton, Rachel [5 ]
Bhandari, Sunil [6 ]
Baker, Richard [7 ]
Berglund, David [8 ]
Carr, Sue [9 ]
Game, David [5 ]
Griffin, Sian [10 ]
Kalra, Philip A. [11 ]
Lewis, Robert [12 ]
Mark, Patrick B. [13 ]
Marks, Stephen D. [14 ]
Macphee, Lain [15 ]
McKane, William [16 ]
Mohaupt, Markus G. [17 ]
Pararajasingam, Ravi [18 ]
Kon, Sui Phin [19 ]
Seron, Daniel [20 ]
Sinha, Manish [21 ]
Tucker, Beatriz [19 ]
Viklicky, Ondrej [22 ]
Lechler, Robert, I [1 ,23 ]
Lord, Graham M. [1 ,3 ,4 ,5 ]
Stahl, Daniel [2 ]
Hernandez-Fuentes, Maria P. [1 ,23 ,24 ]
机构
[1] Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England
[2] Kings Coll London, Inst Psychiat Psychol & Neurosci, Biostat & Hlth Informat Dept, 16 Crespigny Pk, London SE5 8AF, England
[3] Guys & St Thomas NHS Fdn Trust, NIHR Biomed Res Ctr, London SE1 9RT, England
[4] Kings Coll London, London SE1 9RT, England
[5] Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England
[6] Hull & East Yorkshire Hosp NHS Trust, Anlaby Rd, Kingston Upon Hull HU3 2JZ, N Humberside, England
[7] St James Univ Hosp, Beckett St, Leeds LS9 7TF, W Yorkshire, England
[8] Uppsala Univ, Dept Immunol Genet & Pathol, Rudbecklab, S-75185 Uppsala, Sweden
[9] Leicester Gen Hosp, Gwendolen Rd, Leicester LE5 4PW, Leics, England
[10] Cardiff & Vale Univ Hlth Board, Cardiff CF14 4XW, S Glam, Wales
[11] Salford Royal NHS Fdn Trust, Stott Ln, Salford M6 8HD, Lancs, England
[12] Queen Alexandra Hosp, Southwick Hill Rd, Portsmouth PO6 3LY, Hants, England
[13] Univ Glasgow, Univ Ave, Glasgow G12 8QQ, Lanark, Scotland
[14] Great Ormond St Hosp Children NHS Fdn Trust, Great Ormond St,London, London WC1N 3JH, England
[15] St George Hosp, Blackshaw Rd, London SW17 0QT, England
[16] Northern Gen Hosp, Herries Rd, Sheffield S5 7AU, S Yorkshire, England
[17] Univ Hosp, Univ Spital Dept Nephrol Hypertens & Clin Pharmac, INSELSPITAL, Freiburgstr 8, CH-3010 Bern, Switzerland
[18] Manchester Royal Infirm, Oxford Rd, Manchester M13 9WL, Lancs, England
[19] Kings Coll Hosp NHS Fdn Trust, Denmark Hill, London SE5 9RS, England
[20] Hosp Univ Vali dHebron, Passeig Vali dHebron 119-129, Barcelona 08035, Spain
[21] Evelina London Childrens Hosp, Westminster Bridge Rd, London SE1 7EH, England
[22] IKEM, Transplantacni Lab, Videnska 1958-9, Prague 14021 4, Czech Republic
[23] Guys Hosp, Kings Hlth Partners, London SE1 9RT, England
[24] UCB Pharma SA, UCB Celltech, Brussels, Belgium
[25] Univ Concepcion, Pharm Fac, Dept Clin Biochem & Immunol, Lab Mol & Translat Immunol, Concepcion, Chile
[26] UCL, London, England
[27] Kings Coll London, Peter Gorer Dept Immunobiol, London, England
基金
英国医学研究理事会;
关键词
Steroid receptor genes; Steroid conversion; Transplantation; Kidney; Tolerance; Chronic rejection; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; INDUCED LEUCINE-ZIPPER; GLUCOCORTICOID RESISTANCE; MINERALOCORTICOID RECEPTOR; RHEUMATOID-ARTHRITIS; DIALYSIS PATIENTS; GENE-EXPRESSION; T-LYMPHOCYTES; VITAMIN-D; CELLS;
D O I
10.1016/j.mce.2018.01.021
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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. (C) 2018 Elsevier B.V. All rights reserved.
引用
收藏
页码:205 / 216
页数:12
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