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

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2018年 / 473卷

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

页码：205 / 216

页数：12

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