Lower levels of FOXP3 are associated with prolonged inflammatory responses in kidney transplant recipients

Frontiers in Immunology

Immunology

Qais W. Saleh¹  Martin Tepel¹  Afsaneh Mohammadnejad² 

[1] Department of Nephrology, Odense University Hospital, Odense, Denmark;Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark;Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark;

关键词: kidney transplantation;    FOXP3;    inflammation;    T regulatory cells;    C reactive protein;    RNA transcripts;    RNA splice variants;   

DOI  :  10.3389/fimmu.2023.1252857

 received in 2023-07-04, accepted in 2023-08-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundImmunosuppressive treatment of kidney transplant recipients is mainly aimed at pro-inflammatory T effector cells, yet they also target the immunosuppressive T regulatory cells. Here, we test the hypothesis that low levels of the master gene regulator of T regulatory cells, forkhead box P3 (FOXP3) splice variants, are associated with prolonged inflammatory responses to stimuli.MethodsFrom blood samples obtained the first – and 29th day post-transplant, we extracted peripheral blood mononuclear cells and measured mRNA levels of Total FOXP3, pre-mature RNA FOXP3 (pre-mRNA FOXP3), full length FOXP3 (FOXP3fl) and, FOXP3 splice variant excluding exon two (FOXP3d2). We defined the primary outcome as the number of days in which C reactive protein (CRP) was above 50 mg/L. CRP levels were gathered in two periods, the first from the second to 29 days post-transplant, and the second from 30 to 57 days post-transplant. The association was tested using adjusted negative binomial regression.ResultsFrom 507 included kidney transplant recipients, 382 recipients had at least one CRP measurement >50 mg/L in the first period, median duration of elevated CRP was 4 days [interquartile range (IQR) 2 to 6]. In the second period, 69 recipients had at least one CRP measurement >50 mg/L, median duration of elevated CRP was 3 days [IQR 2 to 5]. In the first period, we found a significant association between lower levels of Total FOXP3 and prolonged duration of CRP elevation, incidence rate ratio 0.61 (95% confidence interval 0.46-0.80), p<0.01.ConclusionLower levels of total FOXP3 mRNA levels in peripheral blood of kidney transplant recipients are associated with prolonged duration of inflammatory responses regardless of the underlying stimuli.

【 授权许可】

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Copyright © 2023 Saleh, Mohammadnejad and Tepel