PMID- 36063053
OWN - NLM
STAT- MEDLINE
DCOM- 20230405
LR  - 20230412
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Print)
IS  - 1462-0324 (Linking)
VI  - 62
IP  - 4
DP  - 2023 Apr 3
TI  - Dendritic cells drive profibrotic inflammation and aberrant T cell polarization 
      in systemic sclerosis.
PG  - 1687-1698
LID - 10.1093/rheumatology/keac489 [doi]
AB  - 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-1beta, 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.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      British Society for Rheumatology.
FAU - Choreno-Parra, Jose Alberto
AU  - Choreno-Parra JA
AD  - Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades 
      Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
AD  - Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, 
      Nuevo Leon, Mexico.
FAU - Cervantes-Rosete, Diana
AU  - Cervantes-Rosete D
AD  - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas 
      y Nutricion Salvador Zubiran, Mexico City, Mexico.
FAU - Jimenez-Alvarez, Luis Armando
AU  - Jimenez-Alvarez LA
AD  - Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades 
      Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
FAU - Ramirez-Martinez, Gustavo
AU  - Ramirez-Martinez G
AD  - Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades 
      Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
FAU - Marquez-Garcia, Jose Eduardo
AU  - Marquez-Garcia JE
AD  - Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades 
      Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
FAU - Cruz-Lagunas, Alfredo
AU  - Cruz-Lagunas A
AD  - Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades 
      Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
FAU - Magana-Sanchez, Ana Yelli
AU  - Magana-Sanchez AY
AD  - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas 
      y Nutricion Salvador Zubiran, Mexico City, Mexico.
FAU - Lima, Guadalupe
AU  - Lima G
AD  - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas 
      y Nutricion Salvador Zubiran, Mexico City, Mexico.
FAU - Lopez-Maldonado, Humberto
AU  - Lopez-Maldonado H
AD  - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas 
      y Nutricion Salvador Zubiran, Mexico City, Mexico.
FAU - Gaytan-Guzman, Emanuel
AU  - Gaytan-Guzman E
AD  - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas 
      y Nutricion Salvador Zubiran, Mexico City, Mexico.
FAU - Caballero, Adrian
AU  - Caballero A
AD  - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas 
      y Nutricion Salvador Zubiran, Mexico City, Mexico.
FAU - Fernandez-Plata, Rosario
AU  - Fernandez-Plata R
AD  - Department of Hospital Epidemiology and Infectious Diseases, Instituto Nacional 
      de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
FAU - Furuzawa-Carballeda, Janette
AU  - Furuzawa-Carballeda J
AD  - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas 
      y Nutricion Salvador Zubiran, Mexico City, Mexico.
FAU - Mendoza-Milla, Criselda
AU  - Mendoza-Milla C
AD  - Laboratorio de Transduccion de Senales, Instituto Nacional de Enfermedades 
      Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
FAU - Navarro-Gonzalez, Maria Del Carmen
AU  - Navarro-Gonzalez MDC
AD  - Laboratorio de Investigacion en Enfermedades Reumaticas, Instituto Nacional de 
      Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
FAU - Llorente, Luis
AU  - Llorente L
AD  - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas 
      y Nutricion Salvador Zubiran, Mexico City, Mexico.
FAU - Zuniga, Joaquin
AU  - Zuniga J
AD  - Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades 
      Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
AD  - Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, 
      Nuevo Leon, Mexico.
FAU - Rodriguez-Reyna, Tatiana Sofia
AU  - Rodriguez-Reyna TS
AD  - Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas 
      y Nutricion Salvador Zubiran, Mexico City, Mexico.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (Cytokines)
SB  - IM
MH  - Humans
MH  - *Scleroderma, Systemic
MH  - Cytokines
MH  - Fibrosis
MH  - Dendritic Cells/pathology
MH  - Inflammation
PMC - PMC10070068
OTO - NOTNLM
OT  - IL-33
OT  - SSc
OT  - Th17
OT  - dendritic cells
OT  - toll-like receptors
EDAT- 2022/09/06 06:00
MHDA- 2023/04/05 06:42
PMCR- 2022/09/05
CRDT- 2022/09/05 09:13
PHST- 2022/08/13 00:00 [accepted]
PHST- 2022/02/12 00:00 [received]
PHST- 2023/04/05 06:42 [medline]
PHST- 2022/09/06 06:00 [pubmed]
PHST- 2022/09/05 09:13 [entrez]
PHST- 2022/09/05 00:00 [pmc-release]
AID - 6692301 [pii]
AID - keac489 [pii]
AID - 10.1093/rheumatology/keac489 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2023 Apr 3;62(4):1687-1698. doi: 
      10.1093/rheumatology/keac489.