title: The pronounced Th17 profile in systemic sclerosis (SSc) together with intracellular expression of TGFbeta and IFNgamma distinguishes SSc phenotypes.
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.
  
  
  RESULTS
  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, TGFbeta and IFNgamma using flow cytometry. Levels of IL-17, IL-6, IL-1alpha 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, IFNgamma and TGFbeta 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-1alpha were increased in all or subsets of SSc patients.
  
  
  CONCLUSIONS
  The combination of IL-17, IFNgamma and TGFbeta 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.
authors.affiliation: Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. tradstake73@gmail.com
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.forename: Lenny
authors.initials: L
authors.lastname: van Bon
authors.forename: Jasper
authors.initials: J
authors.lastname: Broen
authors.forename: Anila
authors.initials: A
authors.lastname: Hussiani
authors.forename: Roger
authors.initials: R
authors.lastname: Hesselstrand
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Wuttge
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Deng
authors.forename: Robbert
authors.initials: R
authors.lastname: Simms
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
authors.forename: Robert
authors.initials: R
authors.lastname: Lafyatis
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012595:Scleroderma, Systemic / Q000175:diagnosis* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens