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Pathogenic Transdif...
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Andersson, Karin,1972Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
(author)
Pathogenic Transdifferentiation of Th17 Cells Contribute to Perpetuation of Rheumatoid Arthritis during Anti-TNF Treatment.
- Article/chapterEnglish2015
Publisher, publication year, extent ...
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2015-06-04
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Springer Science and Business Media LLC,2015
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/226723
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https://gup.ub.gu.se/publication/226723URI
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https://doi.org/10.2119/molmed.2015.00057DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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T-helper cells producing interleukin (IL)-17A and IL-17F cytokines (Th17 cells) are considered the source of autoimmunity in rheumatoid arthritis (RA). In this study, we characterized specific pathogenic features of Th17 cells in RA. By using nano-string technology, we analyzed transcription of 419 genes in the peripheral blood CCR6(+)CXCR3(-) CD4(+) cells of 14 RA patients and 6 healthy controls and identified 109 genes discriminating Th17 cells of RA patients from the controls. Th17 cells of RA patients had an aggressive pathogenic profile and in addition to signature cytokines IL-17, IL-23 and IL-21, and transcriptional regulators RAR-related orphan receptor gamma of T cells (RORγt) and Janus kinase 2 (JAK2), they produced high levels of IL-23R, C-C chemokine ligand type 20 (CCL20), granulocyte-monocyte colony-stimulating factor (GM-CSF ) and transcription factor Tbet required for synovial homing. We showed that Th17 cells are enriched with Helios-producing Foxp3- and IL2RA-deficient cells, indicating altered regulatory profile. The follicular T-helper (Tfh) cells presented a functional profile of adaptor molecules, transcriptional regulator Bcl-6 and B-cell activating cytokines IL-21, IL-31 and leukemia inhibitory factor (LIF ). We observed that anti-tumor necrosis factor (TNF) treatment had a limited effect on the transcription signature of Th17 cells. Patients in remission retained the machinery of receptors (IL-23R and IL-1R1), proinflammatory cytokines (IL-17F, IL-23, IL-21 and TNF ) and adaptor molecules (C-X-C chemokine receptor 5 [CXCR5] and cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]), essential for efficient transdifferentiation and accumulation of Th17 cells. This study convincingly shows that the peripheral blood CCR6(+)CXCR3(-) CD4(+) cells of RA patients harbor pathogenic subsets of Th17 and Tfh cells, which may transdifferentiate from Tregs and contribute to perpetuation of the disease.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Cavallini, Nicola,1978Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xcavni
(author)
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Hu, Dan
(author)
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Brisslert, Mikael,1974Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xbrimi
(author)
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Cialic, Ron
(author)
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Valadi, Hadi,1963Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xvalha
(author)
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Erlandsson, Malin,1972Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xerlma
(author)
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Silfverswärd Lindblad, Sofia,1980Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xsilso
(author)
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Pullerits, Rille,1969Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xpulri
(author)
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Kuchroo, Vijay K
(author)
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Weiner, Howard L
(author)
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Bokarewa, Maria,1963Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xbokma
(author)
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Göteborgs universitetInstitutionen för medicin, avdelningen för reumatologi och inflammationsforskning
(creator_code:org_t)
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In:Molecular medicine (Cambridge, Mass.): Springer Science and Business Media LLC21, s. 536-431528-36581076-1551
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