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Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory act...

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Autores principales: Laranjeira, Paula, Pedrosa, Mónia, Duarte, Cátia, Pedreiro, Susana, Antunes, Brígida, Ribeiro, Tânia, dos Santos, Francisco, Martinho, António, Fardilha, Margarida, Domingues, M. Rosário, Abecasis, Manuel, Pereira da Silva, José António, Paiva, Artur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880255/
https://www.ncbi.nlm.nih.gov/pubmed/35214136
http://dx.doi.org/10.3390/pharmaceutics14020404
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author Laranjeira, Paula
Pedrosa, Mónia
Duarte, Cátia
Pedreiro, Susana
Antunes, Brígida
Ribeiro, Tânia
dos Santos, Francisco
Martinho, António
Fardilha, Margarida
Domingues, M. Rosário
Abecasis, Manuel
Pereira da Silva, José António
Paiva, Artur
author_facet Laranjeira, Paula
Pedrosa, Mónia
Duarte, Cátia
Pedreiro, Susana
Antunes, Brígida
Ribeiro, Tânia
dos Santos, Francisco
Martinho, António
Fardilha, Margarida
Domingues, M. Rosário
Abecasis, Manuel
Pereira da Silva, José António
Paiva, Artur
author_sort Laranjeira, Paula
collection PubMed
description Rheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory action of human bone marrow (BM)-MSCs on myeloid dendritic cells (mDCs) and monocytes, especially on cytokines/chemokines involved in RA physiopathology. For that, LPS plus IFNγ-stimulated peripheral blood mononuclear cells from RA patients (n = 12) and healthy individuals (n = 6) were co-cultured with allogeneic BM-MSCs. TNF-α, CD83, CCR7 and MIP-1β protein levels were assessed in mDCs, classical, intermediate, and non-classical monocytes. mRNA expression of other cytokines/chemokines was also evaluated. BM-MSCs effectively reduced TNF-α, CD83, CCR7 and MIP-1β protein levels in mDCs and all monocyte subsets, in RA patients. The inhibition of TNF-α production was mainly achieved by the reduction of the percentage of cellsproducing this cytokine. BM-MSCs exhibited a remarkable suppressive action over antigen-presenting cells from RA patients, potentially affecting their ability to stimulate the immune adaptive response at different levels, by hampering their migration to the lymph node and the production of proinflammatory cytokines and chemokines. Accordingly, MSC-based therapies can be a valuable approach for RA treatment, especially for non-responder patients.
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spelling pubmed-88802552022-02-26 Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis Laranjeira, Paula Pedrosa, Mónia Duarte, Cátia Pedreiro, Susana Antunes, Brígida Ribeiro, Tânia dos Santos, Francisco Martinho, António Fardilha, Margarida Domingues, M. Rosário Abecasis, Manuel Pereira da Silva, José António Paiva, Artur Pharmaceutics Article Rheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory action of human bone marrow (BM)-MSCs on myeloid dendritic cells (mDCs) and monocytes, especially on cytokines/chemokines involved in RA physiopathology. For that, LPS plus IFNγ-stimulated peripheral blood mononuclear cells from RA patients (n = 12) and healthy individuals (n = 6) were co-cultured with allogeneic BM-MSCs. TNF-α, CD83, CCR7 and MIP-1β protein levels were assessed in mDCs, classical, intermediate, and non-classical monocytes. mRNA expression of other cytokines/chemokines was also evaluated. BM-MSCs effectively reduced TNF-α, CD83, CCR7 and MIP-1β protein levels in mDCs and all monocyte subsets, in RA patients. The inhibition of TNF-α production was mainly achieved by the reduction of the percentage of cellsproducing this cytokine. BM-MSCs exhibited a remarkable suppressive action over antigen-presenting cells from RA patients, potentially affecting their ability to stimulate the immune adaptive response at different levels, by hampering their migration to the lymph node and the production of proinflammatory cytokines and chemokines. Accordingly, MSC-based therapies can be a valuable approach for RA treatment, especially for non-responder patients. MDPI 2022-02-12 /pmc/articles/PMC8880255/ /pubmed/35214136 http://dx.doi.org/10.3390/pharmaceutics14020404 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Laranjeira, Paula
Pedrosa, Mónia
Duarte, Cátia
Pedreiro, Susana
Antunes, Brígida
Ribeiro, Tânia
dos Santos, Francisco
Martinho, António
Fardilha, Margarida
Domingues, M. Rosário
Abecasis, Manuel
Pereira da Silva, José António
Paiva, Artur
Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis
title Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis
title_full Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis
title_fullStr Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis
title_full_unstemmed Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis
title_short Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis
title_sort human bone marrow mesenchymal stromal/stem cells regulate the proinflammatory response of monocytes and myeloid dendritic cells from patients with rheumatoid arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880255/
https://www.ncbi.nlm.nih.gov/pubmed/35214136
http://dx.doi.org/10.3390/pharmaceutics14020404
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