Micro RNA-98 suppresses interleukin-10 in peripheral B cells in patient post-cardio transplantation

Abstract

The immune tolerance to the transplant heart survival is critical. Regulatory B cells are one of the major immune regulatory cell populations in the immune tolerance. Micro RNAs (miR) can regulate the activities of immune cells, such as the expression of interleukin (IL)-10 by B cells. This study tests a hypothesis that micro RNA (miR)-98 plays a role in the regulation of interleukin (IL)-10 expression in B cells (B10 cell) after heart transplantation. In this study, the peripheral blood samples were collected from patients before and after heart transplantation. The expression of miR-98 and IL-10 in B cells was assessed by real time RT-PCR. An allograft heart transplantation mouse model was developed. We observed that after heart transplantation, the frequency of peripheral B10 cell and the IL-10 mRNA levels in peripheral B cells were significantly decreased, the levels of miR-98 were increased in peripheral B cells and the serum levels of cortisol were increased in the patients. Treating naive B cells with cortisol in the culture suppressed the expression of IL-10 in B cells, which was abolished by knocking down the miR-98 gene. Administration with anti-miR-98, or cortisol inhibitor, or adoptive transfer with B10 cells, significantly enhanced the survival rate and time of mice received allograft heart transplantation. In conclusion, the enhancement of serum cortisol affects the immune tolerant feature of B cells, which can be attenuated by anti-miR-98-carrying liposomes.

Lentivirus-mediated IL-10-expressing Bone Marrow Mesenchymal Stem Cells promote corneal allograft survival via upregulating lncRNA 003946 in a rat model of corneal allograft rejection

“…IL-10, as a potent suppressor of inflammation, facilitates immune tolerance after organ transplantation 34 , 35 . It inhibits maturation of APCs and activation of monocyte-/macrophage-dependent T cells.…”

Role of microRNAs in Immune Regulation with Translational and Clinical Applications

“…Prolonged survival of rat cardiac allografts following the intrathymic and intravenous injection of MSCs was associated with the down-regulation of miR-155 expression [204]. Production of IL-10 by peripheral B-cells was suppressed by miR-98 following cardiac transplantation, that was successfully inhibited by the administration of anti-miR-98, resulting in improved survival of mice received allografts [205]. Combined evaluation of circulating miR-144-3p and miR-652-3p can be applied as biomarkers for acute cellular rejection in heart transplanted patients [206].…”

The Epigenetic Role of MiRNAs in Endocrine Crosstalk Between the Cardiovascular System and Adipose Tissue: A Bidirectional View

“…In a murine model for cardiac allograft transplantation, miR-98 plays a role in regulating interleukin (IL)-10 expression in B cells (B10 cell) after heart transplantation. The miR-98 inhibition, cortisol inhibition, and transfer with B10 cells enhanced the survival rate and time of transplanted mice ( Song et al, 2017 ). In the first atlas of miRNA profile using internal mammary artery from 192 CAD disease patients, miR-98 was significantly correlated with acute myocardial infarction occurrence, suggesting that this AT-enriched miRNA is also related to the regulation of cardiac function ( Neiburga et al, 2021 ).…”