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Dendritic cells drive profibrotic inflammation and aberrant T cell polarization in systemic sclerosis
OBJECTIVES: SSc is a devastating autoimmune disease characterized by fibrosis and obliterative vasculopathy affecting the skin and visceral organs. While the processes mediating excessive extracellular matrix deposition and fibroblast proliferation are clear, the exact link between autoimmunity and...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070068/ https://www.ncbi.nlm.nih.gov/pubmed/36063053 http://dx.doi.org/10.1093/rheumatology/keac489 |
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author | Choreño-Parra, José Alberto Cervantes-Rosete, Diana Jiménez-Álvarez, Luis Armando Ramírez-Martínez, Gustavo Márquez-García, José Eduardo Cruz-Lagunas, Alfredo Magaña-Sánchez, Ana Yelli Lima, Guadalupe López-Maldonado, Humberto Gaytán-Guzmán, Emanuel Caballero, Adrian Fernández-Plata, Rosario Furuzawa-Carballeda, Janette Mendoza-Milla, Criselda Navarro-González, Maria del Carmen Llorente, Luis Zúñiga, Joaquín Rodríguez-Reyna, Tatiana Sofía |
author_facet | Choreño-Parra, José Alberto Cervantes-Rosete, Diana Jiménez-Álvarez, Luis Armando Ramírez-Martínez, Gustavo Márquez-García, José Eduardo Cruz-Lagunas, Alfredo Magaña-Sánchez, Ana Yelli Lima, Guadalupe López-Maldonado, Humberto Gaytán-Guzmán, Emanuel Caballero, Adrian Fernández-Plata, Rosario Furuzawa-Carballeda, Janette Mendoza-Milla, Criselda Navarro-González, Maria del Carmen Llorente, Luis Zúñiga, Joaquín Rodríguez-Reyna, Tatiana Sofía |
author_sort | Choreño-Parra, José Alberto |
collection | PubMed |
description | OBJECTIVES: SSc is a devastating autoimmune disease characterized by fibrosis and obliterative vasculopathy affecting the skin and visceral organs. While the processes mediating excessive extracellular matrix deposition and fibroblast proliferation are clear, the exact link between autoimmunity and fibrosis remains elusive. Th17 cells have been proposed as critical drivers of profibrotic inflammation during SSc, but little is known about the immune components supporting their pathogenic role. Our aim was to determine cytokine responses of stimulated monocyte-derived dendritic cells (Mo-DCs) and to determine how they influence T-cell cytokine production in SSc. MATERIAL AND METHODS: Dendritic cells (DCs) activate and shape T cell differentiation by producing polarizing cytokines. Hence, we investigated the cytokine responses of monocyte-derived DCs (Mo-DCs) from patients with limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc) and healthy controls (HCs) after stimulation with toll-like receptor (TLR) agonists. Also, using co-culture assays, we analysed T cell subpopulations after contact with autologous TLR-activated Mo-DCs. RESULTS: In general, we observed an increased production of Th17-related cytokines like IL-1β, IL-17F, IL-21 and IL-22 by SSc compared with HC Mo-DCs, with variations between lcSSc vs dcSSc and early- vs late-stage subgroups. Noticeably, we found a significant increment in IL-33 production by Mo-DCs in all SSc cases regardless of their clinical phenotype. Strikingly, T cells displayed Th2, Th17 and dual Th2–Th17 phenotypes after exposure to autologous TLR-stimulated Mo-DCs from SSc patients but not HCs. These changes were pronounced in individuals with early-stage dcSSc and less significant in the late-stage lcSSc subgroup. CONCLUSIONS: Our findings suggest that functional alterations of DCs promote immune mechanisms favouring the aberrant T cell polarization and profibrotic inflammation behind clinical SSc heterogeneity. |
format | Online Article Text |
id | pubmed-10070068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-100700682023-04-05 Dendritic cells drive profibrotic inflammation and aberrant T cell polarization in systemic sclerosis Choreño-Parra, José Alberto Cervantes-Rosete, Diana Jiménez-Álvarez, Luis Armando Ramírez-Martínez, Gustavo Márquez-García, José Eduardo Cruz-Lagunas, Alfredo Magaña-Sánchez, Ana Yelli Lima, Guadalupe López-Maldonado, Humberto Gaytán-Guzmán, Emanuel Caballero, Adrian Fernández-Plata, Rosario Furuzawa-Carballeda, Janette Mendoza-Milla, Criselda Navarro-González, Maria del Carmen Llorente, Luis Zúñiga, Joaquín Rodríguez-Reyna, Tatiana Sofía Rheumatology (Oxford) Basic Science OBJECTIVES: SSc is a devastating autoimmune disease characterized by fibrosis and obliterative vasculopathy affecting the skin and visceral organs. While the processes mediating excessive extracellular matrix deposition and fibroblast proliferation are clear, the exact link between autoimmunity and fibrosis remains elusive. Th17 cells have been proposed as critical drivers of profibrotic inflammation during SSc, but little is known about the immune components supporting their pathogenic role. Our aim was to determine cytokine responses of stimulated monocyte-derived dendritic cells (Mo-DCs) and to determine how they influence T-cell cytokine production in SSc. MATERIAL AND METHODS: Dendritic cells (DCs) activate and shape T cell differentiation by producing polarizing cytokines. Hence, we investigated the cytokine responses of monocyte-derived DCs (Mo-DCs) from patients with limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc) and healthy controls (HCs) after stimulation with toll-like receptor (TLR) agonists. Also, using co-culture assays, we analysed T cell subpopulations after contact with autologous TLR-activated Mo-DCs. RESULTS: In general, we observed an increased production of Th17-related cytokines like IL-1β, IL-17F, IL-21 and IL-22 by SSc compared with HC Mo-DCs, with variations between lcSSc vs dcSSc and early- vs late-stage subgroups. Noticeably, we found a significant increment in IL-33 production by Mo-DCs in all SSc cases regardless of their clinical phenotype. Strikingly, T cells displayed Th2, Th17 and dual Th2–Th17 phenotypes after exposure to autologous TLR-stimulated Mo-DCs from SSc patients but not HCs. These changes were pronounced in individuals with early-stage dcSSc and less significant in the late-stage lcSSc subgroup. CONCLUSIONS: Our findings suggest that functional alterations of DCs promote immune mechanisms favouring the aberrant T cell polarization and profibrotic inflammation behind clinical SSc heterogeneity. Oxford University Press 2022-09-05 /pmc/articles/PMC10070068/ /pubmed/36063053 http://dx.doi.org/10.1093/rheumatology/keac489 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Basic Science Choreño-Parra, José Alberto Cervantes-Rosete, Diana Jiménez-Álvarez, Luis Armando Ramírez-Martínez, Gustavo Márquez-García, José Eduardo Cruz-Lagunas, Alfredo Magaña-Sánchez, Ana Yelli Lima, Guadalupe López-Maldonado, Humberto Gaytán-Guzmán, Emanuel Caballero, Adrian Fernández-Plata, Rosario Furuzawa-Carballeda, Janette Mendoza-Milla, Criselda Navarro-González, Maria del Carmen Llorente, Luis Zúñiga, Joaquín Rodríguez-Reyna, Tatiana Sofía Dendritic cells drive profibrotic inflammation and aberrant T cell polarization in systemic sclerosis |
title | Dendritic cells drive profibrotic inflammation and aberrant T cell polarization in systemic sclerosis |
title_full | Dendritic cells drive profibrotic inflammation and aberrant T cell polarization in systemic sclerosis |
title_fullStr | Dendritic cells drive profibrotic inflammation and aberrant T cell polarization in systemic sclerosis |
title_full_unstemmed | Dendritic cells drive profibrotic inflammation and aberrant T cell polarization in systemic sclerosis |
title_short | Dendritic cells drive profibrotic inflammation and aberrant T cell polarization in systemic sclerosis |
title_sort | dendritic cells drive profibrotic inflammation and aberrant t cell polarization in systemic sclerosis |
topic | Basic Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070068/ https://www.ncbi.nlm.nih.gov/pubmed/36063053 http://dx.doi.org/10.1093/rheumatology/keac489 |
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