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

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

Qais W Saleh  1   2 , Afsaneh Mohammadnejad  3 , Martin Tepel  4   5
Affiliations

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

Qais W Saleh et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Overview of cohorts used for the analysis and of acquired materials, the source of the material and the methods used to measure FOXP3 in each cohort. FOXP3: Forkhead box P3. PBMC: peripheral blood mononuclear cells. MoMoTx: the molecular monitoring after kidney transplantation project. qPCR: quantitative polymerase chain reaction.
Figure 2
Figure 2
Forkhead box P3 transcript levels in female and male (A) healthy kidney donor, (B) pre-transplant (Tx) samples of kidney transplant recipients, (C) first day post-transplant samples of kidney transplant recipients, and (D) 29 days post-transplant samples of kidney transplant recipients.
Figure 3
Figure 3
Percentage of kidney transplant recipients according to fold difference of FOXP3 transcript variant expression relative to healthy kidney donor mean FOXP3 expression (dashed line).
See this image and copyright information in PMC

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