Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes

Bibliographic Details
Main Author: Ferreira, Beatriz H.
Publication Date: 2025
Other Authors: Mazeda, Carolina, Dourado, Eduardo, Simões, João L., Prata, Ana Rita, Argüello, Rafael J., Duarte, Iola F., Pierre, Philippe, Almeida, Catarina R.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/181543
Summary: Funding Information: This work was supported by the World Scleroderma Foundation and Edith Busch Stiftung (the EBF and WSF Research Grant Programme 2022\u20132023). Work developed within the scope of iBiMED \u2013 Institute of Biomedicine (references UIDB/04501/2020, DOI https://doi.org/10.54499/UIDB/04501/2020 , UIDP/04501/2020, DOI https://doi.org/10.54499/UIDP/04501/2020 ), CICECO \u2013 Aveiro Institute of Materials (UIDB/50011/2020, DOI https://doi.org/10.54499/UIDB/50011/2020 ; UIDP/50011/2020, DOI https://doi.org/10.54499/UIDP/50011/2020 & LA/P/0006/2020, DOI https://doi.org/10.54499/LA/P/0006/2020 ), and LAQV-REQUIMTE (LA/P/0008/202, DOI https://doi.org/10.54499/LA/P/0008/2020 ; UIDP/50006/2020, DOI https://doi.org/10.54499/UIDP/50006/2020 ; UIDB/50006/2020, DOI10.54499/UIDB/50006/2020) and the project with the reference 2022.03217.PTDC (DOI https://doi.org/10.54499/2022.03217.PTDC ), financially supported by national funds (OE), through Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia (FCT)/MCTES. FCT is also acknowledged for the individual grant to B.H.F. (SFRH/BD/144706/2019; DOI https://doi.org/10.54499/SFRH/BD/144706/2019 ) and the research contract under the Scientific Employment Stimulus to I.F.D. (CEECIND/02387/2018). Publisher Copyright: © The Author(s) 2025.
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spelling Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypesDendritic cellsImmunometabolismPlasmacytoid dendritic cellsSclerodermaSystemic sclerosisRheumatologyImmunology and AllergyImmunologyFunding Information: This work was supported by the World Scleroderma Foundation and Edith Busch Stiftung (the EBF and WSF Research Grant Programme 2022\u20132023). Work developed within the scope of iBiMED \u2013 Institute of Biomedicine (references UIDB/04501/2020, DOI https://doi.org/10.54499/UIDB/04501/2020 , UIDP/04501/2020, DOI https://doi.org/10.54499/UIDP/04501/2020 ), CICECO \u2013 Aveiro Institute of Materials (UIDB/50011/2020, DOI https://doi.org/10.54499/UIDB/50011/2020 ; UIDP/50011/2020, DOI https://doi.org/10.54499/UIDP/50011/2020 & LA/P/0006/2020, DOI https://doi.org/10.54499/LA/P/0006/2020 ), and LAQV-REQUIMTE (LA/P/0008/202, DOI https://doi.org/10.54499/LA/P/0008/2020 ; UIDP/50006/2020, DOI https://doi.org/10.54499/UIDP/50006/2020 ; UIDB/50006/2020, DOI10.54499/UIDB/50006/2020) and the project with the reference 2022.03217.PTDC (DOI https://doi.org/10.54499/2022.03217.PTDC ), financially supported by national funds (OE), through Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia (FCT)/MCTES. FCT is also acknowledged for the individual grant to B.H.F. (SFRH/BD/144706/2019; DOI https://doi.org/10.54499/SFRH/BD/144706/2019 ) and the research contract under the Scientific Employment Stimulus to I.F.D. (CEECIND/02387/2018). Publisher Copyright: © The Author(s) 2025.Background: Plasmacytoid dendritic cells (pDCs) play a key role in systemic sclerosis (SSc) pathophysiology. However, despite the recognised importance of metabolic reprogramming for pDC function, their metabolic profile in SSc remains to be elucidated. Thus, our study aimed to explore the metabolic profile of pDCs in SSc and their potential contribution to the disease. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of healthy donors and SSc patients. SCENITH™, a single-cell flow cytometry-based method, was applied to infer the metabolic profile of circulating pDCs from patients with SSc. pDCs (CD304+ Lin−) at steady-state or stimulated with CpG A were analysed. Toll-like receptor (TLR)9 activation was confirmed by ribosomal protein S6 phosphorylation. Results: Circulating pDCs from ten healthy donors and fourteen SSc patients were analysed. pDCs from anti-centromere antibody-positive (ACA+) patients displayed higher mitochondrial dependence and lower glycolytic capacity than those from anti-topoisomerase I antibody-positive (ATA+) patients. Furthermore, cells from both ACA+ patients and limited cutaneous SSc (lcSSc) patients showed a stronger response towards TLR9 activation than cells from ATA+, anti-RNA polymerase III antibody-positive (ARA+) or diffuse cutaneous SSc (dcSSc) patients. Conclusions: An innovative single cell flow cytometry-based methodology was applied to analyse the metabolic profile of pDCs from SSc patients. Our results suggest that pDCs from ACA+ patients rely more on oxidative phosphorylation (OXPHOS) and are more responsive to external stimuli, whereas pDCs from ATA+ patients may exhibit a more activated or exhausted profile.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNFerreira, Beatriz H.Mazeda, CarolinaDourado, EduardoSimões, João L.Prata, Ana RitaArgüello, Rafael J.Duarte, Iola F.Pierre, PhilippeAlmeida, Catarina R.2025-03-27T21:12:58Z2025-022025-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/181543eng1478-6354PURE: 111918125https://doi.org/10.1186/s13075-025-03500-3info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-31T02:07:44Zoai:run.unl.pt:10362/181543Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T04:42:36.628723Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes
title Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes
spellingShingle Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes
Ferreira, Beatriz H.
Dendritic cells
Immunometabolism
Plasmacytoid dendritic cells
Scleroderma
Systemic sclerosis
Rheumatology
Immunology and Allergy
Immunology
title_short Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes
title_full Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes
title_fullStr Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes
title_full_unstemmed Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes
title_sort Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes
author Ferreira, Beatriz H.
author_facet Ferreira, Beatriz H.
Mazeda, Carolina
Dourado, Eduardo
Simões, João L.
Prata, Ana Rita
Argüello, Rafael J.
Duarte, Iola F.
Pierre, Philippe
Almeida, Catarina R.
author_role author
author2 Mazeda, Carolina
Dourado, Eduardo
Simões, João L.
Prata, Ana Rita
Argüello, Rafael J.
Duarte, Iola F.
Pierre, Philippe
Almeida, Catarina R.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Ferreira, Beatriz H.
Mazeda, Carolina
Dourado, Eduardo
Simões, João L.
Prata, Ana Rita
Argüello, Rafael J.
Duarte, Iola F.
Pierre, Philippe
Almeida, Catarina R.
dc.subject.por.fl_str_mv Dendritic cells
Immunometabolism
Plasmacytoid dendritic cells
Scleroderma
Systemic sclerosis
Rheumatology
Immunology and Allergy
Immunology
topic Dendritic cells
Immunometabolism
Plasmacytoid dendritic cells
Scleroderma
Systemic sclerosis
Rheumatology
Immunology and Allergy
Immunology
description Funding Information: This work was supported by the World Scleroderma Foundation and Edith Busch Stiftung (the EBF and WSF Research Grant Programme 2022\u20132023). Work developed within the scope of iBiMED \u2013 Institute of Biomedicine (references UIDB/04501/2020, DOI https://doi.org/10.54499/UIDB/04501/2020 , UIDP/04501/2020, DOI https://doi.org/10.54499/UIDP/04501/2020 ), CICECO \u2013 Aveiro Institute of Materials (UIDB/50011/2020, DOI https://doi.org/10.54499/UIDB/50011/2020 ; UIDP/50011/2020, DOI https://doi.org/10.54499/UIDP/50011/2020 & LA/P/0006/2020, DOI https://doi.org/10.54499/LA/P/0006/2020 ), and LAQV-REQUIMTE (LA/P/0008/202, DOI https://doi.org/10.54499/LA/P/0008/2020 ; UIDP/50006/2020, DOI https://doi.org/10.54499/UIDP/50006/2020 ; UIDB/50006/2020, DOI10.54499/UIDB/50006/2020) and the project with the reference 2022.03217.PTDC (DOI https://doi.org/10.54499/2022.03217.PTDC ), financially supported by national funds (OE), through Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia (FCT)/MCTES. FCT is also acknowledged for the individual grant to B.H.F. (SFRH/BD/144706/2019; DOI https://doi.org/10.54499/SFRH/BD/144706/2019 ) and the research contract under the Scientific Employment Stimulus to I.F.D. (CEECIND/02387/2018). Publisher Copyright: © The Author(s) 2025.
publishDate 2025
dc.date.none.fl_str_mv 2025-03-27T21:12:58Z
2025-02
2025-02-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/181543
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dc.language.iso.fl_str_mv eng
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