Year-end Sale % OFF 
Abstract
BackgroundSystemic 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 FindingsPatients 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 IFNγ using flow cytometry. Levels of IL-17, IL-6, IL-1α 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, IFNγ 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-1α were increased in all or subsets of SSc patients.Conclusion and SignificanceThe combination of IL-17, IFNγ 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.
Highlights
Systemic Sclerosis (SSc) is a complex inflammatory autoimmune disease characterized by excessive deposition of matrix molecules, leading to fibrosis of multiple organs including the skin, lungs, heart and gastrointestinal tract, and often leading to severe morbidity and premature death
The combination of IL-17, IFNc and TGFb 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
Summary
Systemic Sclerosis (SSc) is a complex inflammatory autoimmune disease characterized by excessive deposition of matrix molecules, leading to fibrosis of multiple organs including the skin, lungs, heart and gastrointestinal tract, and often leading to severe morbidity and premature death. Alterations in cellular immunity are typified by aberrant T cell biology both in the skin as well as circulation of SSc patients. CD4+ T cells are increased in the circulation of SSc patients [1,2] whereas NKT cells and c/d T cells are decreased [3]. Lesional skin from SSc patients displays various features consistent with T cell activation [1,4,5]. T cell biology was altered in SSc in that the secretion of various inflammatory mediators is markedly increased [6,7]. We investigated whether the recently discovered Th17 pattern was present in SSc
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
