Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs

Beigrezaei, Sara; Fante, Claudia Del; Morosini, Monica; Berezhinskiy, Hatice Oya; Auner, S.; Cattaneo, Elena; Zoppa, Matteo Della; Pandolfi, Laura; Cacciatore, Rosalia; Perotti, Cesare; Höetzenecker, Konrad; Jaksch, Péter; Benazzo, Alberto; Meloni, Federica

doi:10.3390/cells11071117

Cited by 5 publications

(10 citation statements)

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“…Following our previous results on the levels of circulating miRNAs [ 12 ], in order to define if ECP effects are mediated by modulation of MNCs in term of differential miRNA expression and release. The present study represents an extension of the previous one [ 12 ] and it regard patients subjected to ECP using the off-line method at the Apheresis Unit of the Immunohaematology and Transfusion Service of our hospital.…”

Section: Resultsmentioning

confidence: 99%

“…For the present study, we selected four miRNAs previously identified as being associated with BOS and/or ECP response in serum [ 12 ] and miRNAs previously reported in proliferation and function regulation of the main immune cell types of the innate and adaptive immunity [ 15 , 16 ]. In particular, we investigated the relative expression of hsa-miR-155-5p, hsa-miR-146a-5p, hsa-miR-31-5p, hsa-miR-181a-3p, hsa-miR-16-5p, hsa-miR-142-3p and hsa-miR-23b-5p, reported to be involved in the regulation of DCs, B ad T cell immunosoppressive properties.…”

Section: Methodsmentioning

confidence: 99%

“…We observed a significant downregulation of circulating hsa-miR-155-5p, hsa-miR-146a-5p and hsa-miR-31-5p in BOS patients at the start of ECP when compared to healthy subjects. In responders, increased miR-155-5p and decreased miR-23b-3p expression levels at 6 months were found [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Exosomal-miRNas expression and growth factors released by mononuclear cells of CLAD patients in response to extracorporeal photopheresis

Bozzini,

Bozza,

Bagnera

et al. 2024

J Transl Med

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Background CLAD (Chronic Lung Allograft Dysfunction) remains a serious complication following lung transplantation. Some evidence shows that portions of Extracorporeal Photopheresis (ECP)-treated patients improve/stabilize their graft function. In spite of that, data concerning molecular mechanisms are still lacking. Aims of our study were to assess whether ECP effects are mediated by Mononuclear Cells (MNCs) modulation in term of microRNAs (miRNAs) expression and growth factors release. Methods Cells from leukapheresis of 16 CLAD patients, at time 0 and 6-months (10 cycles), were cultured for 48h ± PHA (10 ug/ml) or LPS (2 ug/ml). Expression levels of miR-146a-5p, miR-155-5p, miR-31-5p, miR181a-5p, miR-142-3p, miR-16-5p and miR-23b-5p in MNCs-exosomes were evaluated by qRT-PCR, while ELISA assessed different growth factors levels on culture supernatants. Results Our result showed miR-142-3p down-regulation (p = 0.02) in MNCs of ECP-patients after the 10 cycles and after LPS stimulation (p = 0.005). We also find miR-146a-5p up-regulation in cells after the 10 cycles stimulated with LPS (p = 0.03). Connective tissue growth factor (CTGF) levels significantly decreased in MNCs supernatant (p = 0.04). The effect of ECP is translated into frequency changes of Dendritic Cell (DC) subpopulations and a slight increase in T regulatory cells (Treg) number and a significant decrease in CTGF release. Conclusions ECP might affect regulatory T cell functions, since both miR-142 and miR-146a have been shown to be involved in the regulation of suppressor regulatory T cell functions and DCs. On the other side ECP, possibly by regulating macrophage activation, is able to significantly down modulate CTGF release.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Exosomal-miRNas expression and growth factors released by mononuclear cells of CLAD patients in response to extracorporeal photopheresis

Bozzini,

Bozza,

Bagnera

et al. 2024

J Transl Med

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“…If the disease progresses or worsens despite treatment, retransplantation remains the ultimate necessary option for BOS. [49] 3) Risk factors for BO. Hypoxemia, mechanical ventilation, shortness of breath, and wheezing are the main risk factors for PIBO.…”

Section: Hotspots and Frontiersmentioning

confidence: 99%

Worldwide Bronchiolitis obliterans research: A bibliometric analysis of the published literature between 2002 and 2022

Zhang

Luo

et al. 2023

Medicine

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Bronchiolitis obliterans (BO) is a rare and irreversible chronic respiratory disease. The diagnosis of BO is challenging, and there still needs to be specific therapies and uniform treatment guidelines available. Research on BO has grown steadily over the past 20 years, and with the continued interest of researchers in this area, a bibliometric study of BO becomes necessary. This topic aims to assess the current state of research in BO over the last 2 decades and to identify research hotspots and emerging directions. Information on BO-related articles were obtained from the Science Citation Index Expand of the Web of Science Core Collection (WOSCC [SCI-E]) database. Citespace (6.1.R6), VOSviewer (1.6.18), and the online bibliometrics website (https://bibliometric.com/) were used for bibliometric analysis mainly to include country/region, institution, author, journal, keywords, and references and to construct visual knowledge network diagrams. A total of 4153 publications from the WOSCC [SCI-E] database were included in this study. Most publications come from the United States, Japan, and Germany, which collaborate relatively more frequently. Research institutions in the United States, especially the University of Washington, published the largest number of BO-related articles. Regarding authors, Vos, R is the most productive author, while Verleden, GM is the most influential in BO. In addition, JOURNAL OF HEART AND LUNG TRANSPLANTATION is the journal with the most published articles. The most cited article is Estenne M, 2002. Based on the clustering analysis of keywords and references, the diagnosis of bronchiolitis obliterans syndrome (BOS), treatment of BOS, and risk factors of BO are the current research hotspots and future research trends. We analyzed the publication trends in BO by bibliometrics and mapped the knowledge network of major contributing countries/regions, institutions, authors, and journals. Current research hotspots were found based on the main keywords and references. The outcome may help researchers identify potential collaborators, collaborating institutions, and hot fronts in BO to enhance collaboration on critical issues and improve the diagnosis and treatment of BO.

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“…Recently, the alteration of Smad-4 has been found in association with miR-155-5p and miR-23b-3p, which resulted in an altered expression in responders to extracorporeal photopheresis [ 141 ].…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

Markers of Bronchiolitis Obliterans Syndrome after Lung Transplant: Between Old Knowledge and Future Perspective

et al. 2022

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Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometric pattern without high-resolution computed tomography (HRCT) evidence of parenchymal opacities. Computed tomography and microCT analysis show abundant small airway obstruction, starting from the fifth generation of airway branching and affecting up to 40–70% of airways. The pathogenesis of BOS remains unclear. It is a multifactorial syndrome that leads to pathological tissue changes and clinical manifestations. Because BOS is associated with the worst long-term survival in LTx patients, many studies are focused on the early identification of BOS. Markers may be useful for diagnosis and for understanding the molecular and immunological mechanisms involved in the onset of BOS. Diagnostic and predictive markers of BOS have also been investigated in various biological materials, such as blood, BAL, lung tissue and extracellular vesicles. The aim of this review was to evaluate the scientific literature on markers of BOS after lung transplant. We performed a systematic review to find all available data on potential prognostic and diagnostic markers of BOS.

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Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs

Cited by 5 publications

References 60 publications

Exosomal-miRNas expression and growth factors released by mononuclear cells of CLAD patients in response to extracorporeal photopheresis

Exosomal-miRNas expression and growth factors released by mononuclear cells of CLAD patients in response to extracorporeal photopheresis

Worldwide Bronchiolitis obliterans research: A bibliometric analysis of the published literature between 2002 and 2022

Markers of Bronchiolitis Obliterans Syndrome after Lung Transplant: Between Old Knowledge and Future Perspective

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