Interleukin-35 is upregulated in systemic sclerosis and its serum levels are associated with early disease
Tomcik M, Zerr P, Palumbo-Zerr K, Storkanova H, Hulejova H, Spiritovic M, Kodet O, Stork J, Becvar R, Vencovsky J, Pavelka K, Filkova M, Distler J, Senolt L (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 54
Pages Range: 2273-82
Journal Issue: 12
DOI: 10.1093/rheumatology/kev260
Abstract
IL-35 is a member of the IL-12 family consisting of p35/IL-12a and EBI3/IL-27b subunits. IL-35 exerts immunomodulatory activities in experimental and human autoimmune inflammatory conditions. Our aim was to assess IL-35 expression in the skin and circulation of SSc patients and to characterize its potential association with SSc-related features.Expression of IL-35 in skin and dermal fibroblasts was quantified by quantitative PCR, immunohistochemistry and immunofluorescence. Serum levels of IL-35 (by ELISA), CRP (by turbidimetry), ANA (by immunofluorescence) and autoantibodies of the ENA complex (by immunoblot) were measured in 40 SSc patients. Serum IL-35 was determined in 40 age- and sex-matched healthy controls.IL-35 expression was increased in SSc skin and dermal fibroblasts in a TGF-?-dependent manner. IL-35 induced an activated phenotype in resting fibroblasts and enhanced the release of collagen. IL-35 serum levels were increased in patients with SSc compared with healthy controls [median 83.9 (interquartile range 45.1-146.1) vs 36.2 (interquartile range 17.2-49.4) pg/ml, P < 0.0001]. Serum IL-35 was negatively correlated with disease duration (r = -0.4339, P = 0.0052). In line with this finding, serum IL-35 was increased in patients with an early SSc pattern on capillaroscopy assessment compared with those with active and late SSc patterns.The present study demonstrates overexpression of IL-35 in SSc skin, dermal fibroblasts and serum. TGF-? induces IL-35, which in turn activates resting fibroblasts and enhances the release of collagen, thereby contributing to aberrant TGF-? signalling in SSc. Increased serum IL-35 is associated with early, inflammatory stages of SSc.
Authors with CRIS profile
Pawel Zerr
Department of Medicine 3 – Rheumatology and Immunology
Jörg Distler
Professur für Molekulare Mechanismen der Organfibrose
Involved external institutions
Czech Republic (CZ)How to cite
APA:
Tomcik, M., Zerr, P., Palumbo-Zerr, K., Storkanova, H., Hulejova, H., Spiritovic, M.,... Senolt, L. (2015). Interleukin-35 is upregulated in systemic sclerosis and its serum levels are associated with early disease. Rheumatology, 54(12), 2273-82. https://dx.doi.org/10.1093/rheumatology/kev260
MLA:
Tomcik, Michal, et al. "Interleukin-35 is upregulated in systemic sclerosis and its serum levels are associated with early disease." Rheumatology 54.12 (2015): 2273-82.
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