Downregulation of miRNA17‚Ä?2 cluster marks VŒ≥9VŒ¥2 T cells from patients with rheumatoid arthritis
Authors: Valentina Orlando
Laura Saieva
Giuliana Guggino
Francesco Ciccia
Francesco Dieli
Marco Pio La Manna
Riccardo Alessandro
Paola Cipriani
Roberto Giacomelli
Piero Ruscitti
Nadia Caccamo
Giovanni Triolo
Journal: Arthritis research & therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: Inflammatory cytokines; Rheumatoid arthritis; miRNA17‚Ä?2; Œ≥Œ¥ T cells.
Affiliations: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Universit√† di Palermo, Palermo, Italy., Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico P. Giaccone, Palermo, Italy., Dipartimento di Biopatologia e Biotecnologie Mediche, Universit√† di Palermo, Palermo, Italy., Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy., Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico P. Giaccone, Palermo, Italy. ., Dipartimento di Biopatologia e Biotecnologie Mediche, Universit√† di Palermo, Palermo, Italy. .

Abstract:  Background: We aimed to evaluate the phenotype, function, and microRNA (miRNA)17-92 cluster expression in VŒ≥9VŒ¥2 T-cell subsets and the correlation with immune response in rheumatoid arthritis (RA) patients. Methods: Peripheral blood from 10 early RA untreated patients and 10 healthy donors (HD) was obtained. Polyclonal VŒ≥9VŒ¥2 T-cell lines were generated and analysed by flow cytometry. Analysis of miRNA17-92 cluster expression was performed by real-time polymerase chain reaction (RT-PCR), and expression of mRNA target genes was also studied. Results: A remarkable change in the distribution of VŒ≥9VŒ¥2 T-cell functional subsets was observed in the peripheral blood of RA patients compared with HD, with an expansion of effector subsets and reduction of naive cells which was accompanied by modifications in proinflammatory cytokine expression. VŒ≥9VŒ¥2 T cells with a TEM (effector memory) phenotype and producing proinflammatory cytokines were correlated with disease activity score (DAS28). The comparison of miRNA expression among VŒ≥9VŒ¥2 T-cell subsets from RA patients and HD showed a lower level of miR-106a-5p and miR-20a-5p, and a higher level of miR-21a-5p, among VŒ≥9VŒ¥2 TEM cells, and a lower level of miR-19b-3p among VŒ≥9VŒ¥2 TCM (central memory) cells was also found. These differentially expressed miRNAs correlated with higher levels of expression of interleukin (IL)-8, IL-6, and PDCD4 genes. Conclusions: Our results provide evidence for a role of miR-106a, miR-19-3p, miR-20a, and miR-21a in the regulation of VŒ≥9VŒ¥2 T-cell function in RA patients and suggest the possibility that the miRNA17-92 family and VŒ≥9VŒ¥2 T cells contribute to the pathogenesis of RA. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A89 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 23 publications have an expression of concern. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable ,