Dominant regulation of long-term allograft survival is mediated by microRNA-142

Abstract

Solid allograft transplantation can be lifesaving at the point of organ failure. However, long-term allograft and patient survival depends on sustained drug-induced immunosuppression. Acute cellular rejection (ACR) occurs in around 25% of heart transplant recipients in the first-year posttransplant despite optimal levels of currently available immunosuppressive therapy, accounting for 10% of mortality in the

MicroRNA-142 Critically Regulates Group 2 Innate Lymphoid Cell Homeostasis and Function

“…Within the immune system, miR-142 plays profound and nonredundant roles in multiple facets of immune cell development, fate, and function (1722). This is concordant with reported aberrations in miR-142 expression during immune-pathologies (2327) and with its critical role in the maintenance of peripheral immune tolerance (28,29). Importantly, miR-142 expression in lymphocytes such as T cells has been associated with anti-inflammatory actions, with downregulation of expression observed in association with activated cell phenotypes (23,30).…”

MicroRNAs as theranostic markers in cardiac allograft transplantation: from murine models to clinical practice

“…The uptake of miR-142-3p into endothelial cells explains its presence in the allografts, and importantly, its increase was also detected in the kidney 78 and liver 79 transplants. Together with the results of the recent study by Anandagoda et al (as discussed in 3.2.4) 71 this raises a potential question whether miR-142-3p may represent a potential universal marker of rejection released to the systemic circulation from T-cells and whether modulating its levels may protect allografts from rejection. This needs to be validated by further studies.…”

“…Even in such a model, the donor's hearts continued to beat for more than 100 days, pointing out the importance of miR-142 in T-cells response to the alloantigens. Specifically, in all models of miR-142 deficiency, an increase in Treg cells subpopulation was observed 71 .…”

“…It was also studied in several human studies by the team of Sukma-Dewi as a potential ACR biomarker (as discussed in 4.2.1) 68 - 70 . In a recent survey of Anandagoda et al, miR-142 was also the main focus, and on several murine models, authors showed that miR-142 is a crucial mediator of both ACR and AMR 71 . Authors first showed and confirmed that both variants of miR-142 (i.e., miR-142-3p and miR-142-5p) are increased in cardiac allografts on days 4 and 8 after the operation and that survival of such allografts is below ten days.…”

Erratum

“…In the article by Anandagoda et al (2020), 1 the part Figures 2A and 3A had incorrect color coding in the published version. The corrected figures are shown below:…”