The pronounced Th17 profile in systemic sclerosis (SSc) together with intracellular expression of TGFbeta and IFNgamma distinguishes SSc phenotypes.
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.
Radstake
Timothy R D J
TR
Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. tradstake73@gmail.com
van Bon
Lenny
L
Broen
Jasper
J
Hussiani
Anila
A
Hesselstrand
Roger
R
Wuttge
Dirk M
DM
Deng
Yanhui
Y
Simms
Robbert
R
Lubberts
Erik
E
Lafyatis
Robert
R
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*
D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens