The Pronounced Th17 Profile in Systemic Sclerosis (SSc) Together with Intracellular Expression of TGFβ and IFNϒ Distinguishes SSc Phenotypes

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dc.contributor.author Radstake, Timothy R. D. J. en_US
dc.contributor.author van Bon, Lenny en_US
dc.contributor.author Broen, Jasper en_US
dc.contributor.author Hussiani, Anila en_US
dc.contributor.author Hesselstrand, Roger en_US
dc.contributor.author Wuttge, Dirk M. en_US
dc.contributor.author Deng, Yanhui en_US
dc.contributor.author Simms, Robbert en_US
dc.contributor.author Lubberts, Erik en_US
dc.contributor.author Lafyatis, Robert en_US
dc.date.accessioned 2012-01-11T22:31:11Z
dc.date.available 2012-01-11T22:31:11Z
dc.date.issued 2009-6-17 en_US
dc.identifier.citation Radstake, Timothy R. D. J., Lenny van Bon, Jasper Broen, Anila Hussiani, Roger Hesselstrand, Dirk M. Wuttge, Yanhui Deng, Robbert Simms, Erik Lubberts, Robert Lafyatis. "The Pronounced Th17 Profile in Systemic Sclerosis (SSc) Together with Intracellular Expression of TGFβ and IFNϒ Distinguishes SSc Phenotypes" PLoS ONE 4(6): e5903. (2009) en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://hdl.handle.net/2144/3308
dc.description.abstract BACKGROUND. Systemic sclerosis (SSc) is an autoimmune disease where controversy on Th1/Th2 balance dominates. We investigated whether the recently discovered Th17 pattern was present in SSc. METHODOLOGY AND PRINCIPAL FINDINGS. Patients were subdivided as having limited cutaneous SSc (lcSSc, n=12) or diffuse cutaneous SSc (dcSSc, n=24). A further arbitrary subdivision was made between early dcSSc (n=11) and late dcSSc (n=13) based upon the duration of disease. As a comparator group 14 healthy controls were studied. CD3+ cells were isolated using FACS and subsequently studied for the expression of CD4, CD8, CD25, CD45Ro, CD45Ra, IL-23, GITR, CD69 and intracellular expression of IL-17, TGFβ and IFNϒ using flow cytometry. Levels of IL-17, IL-6, IL-1a and IL-23 were measured using Bioplex assays. SSc patients had more and more activated CD4+ cells. In addition, CD4, CD45Ro and CD45Ra cells from all SSc patients highly expressed the IL23R, which was associated with a higher IL-17 expression as well. In contrast, IFNϒ and TGFβ were selectively up regulated in SSc subsets. In line with these observation, circulating levels of IL-17 inducing cytokines IL-6, IL-23 and IL-1a were increased in all or subsets of SSc patients. CONCLUSION AND SIGNIFICANCE. The combination of IL-17, IFNϒ and TGFβ levels in CD45Ro and CD45Ra cells from SSc patients is useful to distinguish between lSSc, ldSSc or edSSc. Blocking Th17 inducing cytokines such as IL-6 and IL-23 may provide a useful tool to intervene in the progression of SSc. en_US
dc.description.sponsorship Niels-Stensen Foundation from The Netherlands; VIDI laureate from the Dutch Organization of Research; National Institutes of Health, (NIAMS U01AR055063); American Society for Scleroderma Research. en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.title The Pronounced Th17 Profile in Systemic Sclerosis (SSc) Together with Intracellular Expression of TGFβ and IFNϒ Distinguishes SSc Phenotypes en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pone.0005903 en_US
dc.identifier.pubmedid 19536281 en_US
dc.identifier.pmcid 2691991 en_US

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