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健康人群和肾移植受者中男性和女性的 FOXP3 剪接变异体表达。

FOXP3 splice variant expression in males and females in healthy populations and in kidney transplant recipients.

机构信息

Department of Nephrology, Odense University Hospital, J. B. Winsløws Vej 4, 5000, Odense, Denmark.

Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 21.3, 5000, Odense C, Denmark.

出版信息

Sci Rep. 2024 May 27;14(1):12112. doi: 10.1038/s41598-024-62149-1.


DOI:10.1038/s41598-024-62149-1
PMID:38802392
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11130272/
Abstract

The forkhead box P3 (FOXP3) transcript is essential for tolerance of alloantigens. Here, we describe the expression of FOXP3 mRNA variants in healthy females and males, and in kidney transplant recipients (KTR). We measured FOXP3 in peripheral blood mononuclear cells from healthy kidney donors (N = 101), and in blood from KTRs (N = 248) before and after transplantation. FOXP3 was measured with quantitative polymerase chain reaction, and differentiated between pre-mature mRNA FOXP3, Total mature FOXP3, FOXP3 in which exon two is spliced, and full length FOXP3. We found similar levels of FOXP3 in healthy female and male kidney donors. We confirmed this result in a publicly available cohort (N = 33) of healthy individuals (GSE97475). Homogenously, female and male KTR FOXP3 levels were similar pre-transplantation, one day post-transplantation and 29 days post-transplantation. This may suggest that kidney transplantation and related immunosuppressive treatments do not influence FOXP3 expression differently in females and males. Finally, fold difference analysis revealed that KTRs express lower levels of mature FOXP3 and higher levels of pre-mature FOXP3 mRNA pre-transplant compared to healthy individuals. This finding may suggest higher pre-mRNA synthesis, lower pre-mRNA degradation, lower spliceosome efficiency or higher degradation of mature FOXP3 mRNA in kidney transplant candidates.

摘要

叉头框蛋白 P3(FOXP3)转录本对于同种异体抗原的耐受性至关重要。在这里,我们描述了 FOXP3 mRNA 变体在健康女性和男性以及肾移植受者(KTR)中的表达。我们测量了健康供肾者(N=101)和肾移植受者(N=248)外周血单个核细胞中的 FOXP3,包括移植前和移植后。使用定量聚合酶链反应(PCR)测量 FOXP3,并区分前体 mRNA FOXP3、总成熟 FOXP3、外显子 2 拼接的 FOXP3 和全长 FOXP3。我们发现健康女性和男性供肾者的 FOXP3 水平相似。我们在一个公开的健康个体队列(N=33)中证实了这一结果(GSE97475)。女性和男性 KTR 的 FOXP3 水平在移植前、移植后 1 天和移植后 29 天相似。这可能表明,肾移植和相关的免疫抑制治疗不会以不同的方式影响女性和男性的 FOXP3 表达。最后,折叠差异分析显示,与健康个体相比,肾移植受者在移植前表达的成熟 FOXP3 水平较低,前体 mRNA FOXP3 水平较高。这一发现可能表明,肾移植候选者中前体 mRNA 的合成更高,前体 mRNA 的降解更低,剪接体效率更低,或成熟 FOXP3 mRNA 的降解更高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad71/11130272/26d45ae0da54/41598_2024_62149_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad71/11130272/db297225f86f/41598_2024_62149_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad71/11130272/8285cec360f9/41598_2024_62149_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad71/11130272/26d45ae0da54/41598_2024_62149_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad71/11130272/db297225f86f/41598_2024_62149_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad71/11130272/8285cec360f9/41598_2024_62149_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad71/11130272/26d45ae0da54/41598_2024_62149_Fig3_HTML.jpg

相似文献

[1]
FOXP3 splice variant expression in males and females in healthy populations and in kidney transplant recipients.

Sci Rep. 2024-5-27

[2]
FOXP3 full length splice variant is associated with kidney allograft tolerance.

Front Immunol. 2024-4-10

[3]
Forkhead box protein 3 mRNA expression in the peripheral blood of kidney-transplant recipients with acute rejection.

Chin Med J (Engl). 2011-6

[4]
Forkhead box P3 (FOXP3) mRNA expression immediately after living-donor liver transplant.

Exp Clin Transplant. 2009-3

[5]
High Expression of FOXP3 mRNA in Blood and Urine as a Predictive Marker in Kidney Transplantation.

Prog Transplant. 2018-6

[6]
Lower levels of FOXP3 are associated with prolonged inflammatory responses in kidney transplant recipients.

Front Immunol. 2023-9-13

[7]
Longitudinal monitoring of mRNA levels of regulatory T cell biomarkers by using non-invasive strategies to predict outcome in renal transplantation.

BMC Nephrol. 2022-2-2

[8]
Comparison of FOXP3 and Interleukin 35 Expression Profiles in Kidney Transplant Recipients With Excellent Long-Term Graft Function and Acute Rejection.

Exp Clin Transplant. 2021-11

[9]
Expression of full-length and splice forms of FoxP3 in rheumatoid arthritis.

Scand J Rheumatol. 2010-8

[10]
Th17 transcription factor RORC2 is inversely correlated with FOXP3 expression in the joints of children with juvenile idiopathic arthritis.

J Rheumatol. 2009-9

引用本文的文献

[1]
Alternative Splicing as a Modulator of the Interferon-Gamma Pathway.

Cancers (Basel). 2025-2-10

本文引用的文献

[1]
Lower levels of FOXP3 are associated with prolonged inflammatory responses in kidney transplant recipients.

Front Immunol. 2023-9-13

[2]
The splicing isoform Foxp3Δ2 differentially regulates tTreg and pTreg homeostasis.

Cell Rep. 2023-8-29

[3]
Co-expression of Foxp3 and Helios facilitates the identification of human T regulatory cells in health and disease.

Front Immunol. 2023

[4]
CD4CD25 T regulatory cells in renal transplantation.

Front Immunol. 2022

[5]
Investigating sex differences in T regulatory cells from cisgender and transgender healthy individuals and patients with autoimmune inflammatory disease: a cross-sectional study.

Lancet Rheumatol. 2022-8-31

[6]
Graft survival differences in kidney transplants related to recipient sex and age.

Front Med (Lausanne). 2022-9-26

[7]
FOXP3 exon 2 controls T stability and autoimmunity.

Sci Immunol. 2022-6-24

[8]
RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients.

Sci Data. 2022-5-9

[9]
Co-Expression of FOXP3FL and FOXP3Δ2 Isoforms Is Required for Optimal Treg-Like Cell Phenotypes and Suppressive Function.

Front Immunol. 2021

[10]
Biological Sex As a Critical Variable in CD4 Effector T Cell Function in Preclinical Models of Multiple Sclerosis.

Antioxid Redox Signal. 2022-7

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