Format

Send to

Choose Destination
PLoS One. 2014 Aug 19;9(8):e105008. doi: 10.1371/journal.pone.0105008. eCollection 2014.

High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis.

Author information

1
Immunology and Allergy, University Hospital and School of Medicine, Geneva, Switzerland; Experimental Laboratory of Immunological and Rheumatologic Researches, IRCSS Istituto Auxologico Italiano, Milan, Italy.
2
Immunology and Allergy, University Hospital and School of Medicine, Geneva, Switzerland; Dermatology, University Hospital and School of Medicine, Geneva, Switzerland.
3
Immunology and Allergy, University Hospital and School of Medicine, Geneva, Switzerland.
4
Dermatology, University Hospital and School of Medicine, Geneva, Switzerland.
5
Institute of Clinica Medica, Ancona, Italy.
6
Rheumatology, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy.
7
Experimental Laboratory of Immunological and Rheumatologic Researches, IRCSS Istituto Auxologico Italiano, Milan, Italy; Division of Rheumatology, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Abstract

BACKGROUND:

High interleukin (IL)-17A levels are characteristically found in the skin of systemic sclerosis (SSc) individuals. Our aim was to investigate whether the dermal expression of IL-17A and related IL-17 family members (i.e. IL-17C, IL-17E and IL-17F) could distinguish fibrotic from healthy skin and could show similarities in SSc and morphea, two disorders with presumed distinct pathogenesis, but characterized by skin fibrosis.

METHODS:

Biopsies were obtained from the involved skin of 14 SSc, 5 morphea and 8 healthy donors (HD) undergoing plastic surgery. Immunohistochemistry/immunofluorescence techniques were coupled to a semi-automated imaging quantification approach to determine the presence of the IL-17 family members in the skin. The in vitro effects induced by the IL-17 family members on fibroblasts from normal and SSc individuals were assessed by ELISA and RIA.

RESULTS:

Positive cells for each of the IL-17 isoforms investigated were present in the dermis of all the individuals tested, though with variable frequencies. SSc individuals had increased frequency of IL-17A+ (p = 0.0237) and decreased frequency of IL-17F+ (p = 0.0127) and IL-17C+ cells (p = 0.0008) when compared to HD. Similarly, morphea individuals had less frequent IL-17C+ cells (p = 0.0186) in their skin but showed similar number of IL-17A+ and IL-17F+ cells when compared to HD. Finally, IL-17E+ cells were more numerous in morphea (p = 0.0109) and tended to be more frequent in SSc than in HD. Fibroblast production of IL-6, MMP-1 and MCP-1 was enhanced in a dose-dependent manner in the presence of IL-17E and IL-17F, but not in the presence of IL-17C. None of the cytokine tested had significant effect on type I collagen production. Of interest, in SSc the frequency of both IL-17A and IL-17F positive cells increased with disease duration.

CONCLUSIONS:

The frequency of IL-17A and IL-17F distinguish SSc to morphea individuals while dermal expression of IL-17C (low) and IL-17E (high) identifies a fibrosis-specific motif. The specific IL-17C/IL-17E cytokine combination may thus play a role in the development of fibrosis.

PMID:
25136988
PMCID:
PMC4138152
DOI:
10.1371/journal.pone.0105008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center