Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/25071
Title: Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients
Authors: Arruda, Lucas Coelho Marlière
Lorenzi, Julio Cesar Cetrulo
Sousa, A P A
Zanette, Dalila Lucíola
Palma, Patricia Vianna Bonini
Panepucci, Rodrigo Alexander
Souza, Doralina Guimarães Brum
Barreira, Amilton Antunes
Covas, Dimas Tadeu
Simões, Belinda Pinto
Silva Junior, Wilson Araújo da
Oliveira, Maria Carolina
Malmegrim, Kelen Cristina Ribeiro
Affilliation: University of São Paulo. Ribeirão Preto Medical School. Regional Blood Center of Ribeirão Preto. Center for Cell-based Therapy. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Regional Blood Center of Ribeirão Preto. Center for Cell-based Therapy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Regional Blood Center of Ribeirão Preto. Center for Cell-based Therapy. Ribeirão Preto, SP, Brazil / Faculty of Medicine. Imperial College London. Division of Brain Sciences. London, UK
University of São Paulo. Ribeirão Preto Medical School. Regional Blood Center of Ribeirão Preto. Center for Cell-based Therapy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Regional Blood Center of Ribeirão Preto. Center for Cell-based Therapy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Regional Blood Center of Ribeirão Preto. Center for Cell-based Therapy. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Division of Hematology. São Paulo, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Hospital das Clínicas. Department of Neuroscience and Behavioral Science. São Paulo, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Hospital das Clínicas. Department of Neuroscience and Behavioral Science. São Paulo, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Regional Blood Center of Ribeirão Preto. Center for Cell-based Therapy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Regional Blood Center of Ribeirão Preto. Center for Cell-based Therapy. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Internal Medicine. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Regional Blood Center of Ribeirão Preto. Center for Cell-based Therapy. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Internal Medicine. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Regional Blood Center of Ribeirão Preto. Center for Cell-based Therapy. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Internal Medicine. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Regional Blood Center of Ribeirão Preto. Center for Cell-based Therapy. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Biochemistry and Immunology. Ribeirão Preto, SP, Brazil / University of São Paulo. School of Pharmaceutical Sciences of Ribeirão Preto. Department of Clinical, Toxicological and Bromatological Analyses. Ribeirão Preto, SP, Brazil
Abstract: Autologous hematopoietic SCT (AHSCT) has been investigated in the past as a therapeutic alternative for multiple sclerosis (MS). Despite advances in clinical management, knowledge about mechanisms involved with clinical remission post transplantation is still limited. Abnormal microRNA and gene expression patterns were described in MS and have been suggested as disease biomarkers and potential therapeutic targets. Here we assessed T- and B-cell reconstitution, microRNAs and immunoregulatory gene expression after AHSCT. Early immune reconstitution was mainly driven by peripheral homeostatic proliferation. AHSCT increased CD4(+)CD25(hi)FoxP3(+) regulatory T-cell counts and expression of CTLA-4 and GITR (glucocorticoid-induced TNFR) on CD4(+)CD25(hi) T cells. We found transient increase in exhausted PD-1(+) T cells and of suppressive CD8(+)CD28(-)CD57(+) T cells. At baseline, CD4(+) and CD8(+) T cells from MS patients presented upregulated miR-16, miR-155 and miR-142-3p and downregulated FOXP3, FOXO1, PDCD1 and IRF2BP2. After transplantation, the expression of FOXP3, FOXO1, PDCD1 and IRF2BP2 increased, reaching control levels at 2 years. Expression of miR-16, miR-155 and miR-142-3p decreased towards normal levels at 6 months post therapy, remaining downregulated until the end of follow-up. These data strongly suggest that AHSCT normalizes microRNA and gene expression, thereby improving the immunoregulatory network. These mechanisms may be important for disease control in the early periods after AHSCT.
Keywords: Multiple sclerosis
Transplantation
Cell Transplantation
MicroRNAs
Humans
keywords: Esclerose múltipla
Transplantes
Transplante de células
MicroRNAs
Humanos
Issue Date: 2015
Publisher: Nature Publishing Group
Citation: ARRUDA, L. C. M. et al. Autologous hematopoietic SCT normalizes miR-16, -155 and -142-3p expression in multiple sclerosis patients. Bone Marrow Transplantation, v. 50, p. 380–389, 2015.
Description: ZANETTE, Dalila Lucíola. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.
DOI: 10.1038/bmt.2014.277
ISSN: 0268-3369
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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