Differentially expressed microRNAs in pre-transplant lung biopsies target immune checkpoint proteins and can predict primary graft dysfunction in lung transplantation
Lung transplantation (LTx) significantly improves outcomes for patients with end-stage respiratory failure. However, primary graft dysfunction (PGD) remains one of the most relevant hurdles. Although PGD is attributed to ischemia-reperfusion injury (IRI), immune responses, primarily T cell-mediated,...
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Elsevier
2025-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844025008953 |
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| author | Vitale Miceli Pia Ferrigno Claudio Centi Claudia Carcione Gioacchin Iannolo Valentina Agnese Giovanna Lo Iacono Rosa Liotta Pier Giulio Conaldi Massimo Pinzani Lavinia De Monte Alessandro Bertani |
| author_facet | Vitale Miceli Pia Ferrigno Claudio Centi Claudia Carcione Gioacchin Iannolo Valentina Agnese Giovanna Lo Iacono Rosa Liotta Pier Giulio Conaldi Massimo Pinzani Lavinia De Monte Alessandro Bertani |
| author_sort | Vitale Miceli |
| collection | DOAJ |
| description | Lung transplantation (LTx) significantly improves outcomes for patients with end-stage respiratory failure. However, primary graft dysfunction (PGD) remains one of the most relevant hurdles. Although PGD is attributed to ischemia-reperfusion injury (IRI), immune responses, primarily T cell-mediated, may play a pivotal role in its pathogenesis. Additionally, innate immune activation following IRI links PGD to adaptive alloimmunity, highlighting the impact of early events on LTx outcomes. Immune checkpoints (ICPs) such as PD-1/PD-L1, CD40/CD40LG, and OX40/OX40L, regulate post-LTx T cell responses, and dysregulation of microRNAs (miRNAs) has been implicated in altering ICP expression, influencing the amplification of immune responses.In this preliminary study, we used the taqMan low-density array (TLDA) cards to investigate miRNA dysregulation's prognostic potential as a PGD marker in pre-transplant back-table lung biopsies. Our analysis revealed differential miRNA expression in donor lung tissues, potentially associated with PGD onset, targeting immune regulatory pathways. Specifically, deregulated miRNAs targeted key ICP proteins, including PD-L1, CD40LG, and OX40L. Moreover, the differential expression of these miRNAs was observed in grafts with future PGD compared to grafts without PGD, suggesting a potential prognostic benefit and a possible role for lung tissue miRNAs in the onset of early graft dysfunction.These findings provide a basis for future investigations into their mechanistic roles and therapeutic potential for PGD. Although based on a limited number of cases, our results imply that miRNAs might be involved in early graft dysfunction. While requiring validation in larger cohorts, our data raise the possibility that the evaluation of the aforementioned markers during the pre-transplant phase, might offer a prognostic benefit in monitoring the onset of PGD. Additionally, the use of compounds that can modulate the function of these molecules could be evaluated for the management of LTx patients. |
| format | Article |
| id | doaj-art-48e48acde2a3456fbe3d926ab4143cf8 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-48e48acde2a3456fbe3d926ab4143cf82025-02-12T05:31:24ZengElsevierHeliyon2405-84402025-02-01114e42515Differentially expressed microRNAs in pre-transplant lung biopsies target immune checkpoint proteins and can predict primary graft dysfunction in lung transplantationVitale Miceli0Pia Ferrigno1Claudio Centi2Claudia Carcione3Gioacchin Iannolo4Valentina Agnese5Giovanna Lo Iacono6Rosa Liotta7Pier Giulio Conaldi8Massimo Pinzani9Lavinia De Monte10Alessandro Bertani11Research Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy; Corresponding author. Department of Research, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Via Tricomi 5, Palermo, 90127, Italy.Division of Thoracic Surgery and Lung Transplantation, Chest Center, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione), Palermo, Italy; UPMCI (University of Pittsburgh Medical Center Italy), Palermo, ItalyResearch Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, ItalyRi.MED Foundation, Palermo, ItalyResearch Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, ItalyResearch Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, ItalyResearch Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, ItalyPathology Unit, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy; UPMCI (University of Pittsburgh Medical Center Italy), Palermo, ItalyResearch Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, ItalyResearch Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, ItalyDivision of Thoracic Surgery and Lung Transplantation, Chest Center, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione), Palermo, ItalyDivision of Thoracic Surgery and Lung Transplantation, Chest Center, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione), Palermo, Italy; UPMCI (University of Pittsburgh Medical Center Italy), Palermo, Italy; Corresponding author. Division of Thoracic Surgery and Lung Transplantation, Chest Center, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), 90127, Palermo, Italy.Lung transplantation (LTx) significantly improves outcomes for patients with end-stage respiratory failure. However, primary graft dysfunction (PGD) remains one of the most relevant hurdles. Although PGD is attributed to ischemia-reperfusion injury (IRI), immune responses, primarily T cell-mediated, may play a pivotal role in its pathogenesis. Additionally, innate immune activation following IRI links PGD to adaptive alloimmunity, highlighting the impact of early events on LTx outcomes. Immune checkpoints (ICPs) such as PD-1/PD-L1, CD40/CD40LG, and OX40/OX40L, regulate post-LTx T cell responses, and dysregulation of microRNAs (miRNAs) has been implicated in altering ICP expression, influencing the amplification of immune responses.In this preliminary study, we used the taqMan low-density array (TLDA) cards to investigate miRNA dysregulation's prognostic potential as a PGD marker in pre-transplant back-table lung biopsies. Our analysis revealed differential miRNA expression in donor lung tissues, potentially associated with PGD onset, targeting immune regulatory pathways. Specifically, deregulated miRNAs targeted key ICP proteins, including PD-L1, CD40LG, and OX40L. Moreover, the differential expression of these miRNAs was observed in grafts with future PGD compared to grafts without PGD, suggesting a potential prognostic benefit and a possible role for lung tissue miRNAs in the onset of early graft dysfunction.These findings provide a basis for future investigations into their mechanistic roles and therapeutic potential for PGD. Although based on a limited number of cases, our results imply that miRNAs might be involved in early graft dysfunction. While requiring validation in larger cohorts, our data raise the possibility that the evaluation of the aforementioned markers during the pre-transplant phase, might offer a prognostic benefit in monitoring the onset of PGD. Additionally, the use of compounds that can modulate the function of these molecules could be evaluated for the management of LTx patients.http://www.sciencedirect.com/science/article/pii/S2405844025008953Lung transplantationPrimary graft dysfunctionmicroRNAImmune checkpointsIschemia-reperfusion injuryPrognostic biomarkers |
| spellingShingle | Vitale Miceli Pia Ferrigno Claudio Centi Claudia Carcione Gioacchin Iannolo Valentina Agnese Giovanna Lo Iacono Rosa Liotta Pier Giulio Conaldi Massimo Pinzani Lavinia De Monte Alessandro Bertani Differentially expressed microRNAs in pre-transplant lung biopsies target immune checkpoint proteins and can predict primary graft dysfunction in lung transplantation Heliyon Lung transplantation Primary graft dysfunction microRNA Immune checkpoints Ischemia-reperfusion injury Prognostic biomarkers |
| title | Differentially expressed microRNAs in pre-transplant lung biopsies target immune checkpoint proteins and can predict primary graft dysfunction in lung transplantation |
| title_full | Differentially expressed microRNAs in pre-transplant lung biopsies target immune checkpoint proteins and can predict primary graft dysfunction in lung transplantation |
| title_fullStr | Differentially expressed microRNAs in pre-transplant lung biopsies target immune checkpoint proteins and can predict primary graft dysfunction in lung transplantation |
| title_full_unstemmed | Differentially expressed microRNAs in pre-transplant lung biopsies target immune checkpoint proteins and can predict primary graft dysfunction in lung transplantation |
| title_short | Differentially expressed microRNAs in pre-transplant lung biopsies target immune checkpoint proteins and can predict primary graft dysfunction in lung transplantation |
| title_sort | differentially expressed micrornas in pre transplant lung biopsies target immune checkpoint proteins and can predict primary graft dysfunction in lung transplantation |
| topic | Lung transplantation Primary graft dysfunction microRNA Immune checkpoints Ischemia-reperfusion injury Prognostic biomarkers |
| url | http://www.sciencedirect.com/science/article/pii/S2405844025008953 |
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