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IL-25 participates in keratinocyte-driven dermal matrix turnover and is reduced in systemic sclerosis epidermis
- Source :
- Rheumatology (Oxford, England). 61(11)
- Publication Year :
- 2021
-
Abstract
- Objectives Evidence shows that dysfunctional SSc keratinocytes contribute to fibrosis by altering dermal homeostasis. Whether IL-25, an IL-17 family member regulating many epidermal functions, takes part in skin fibrosis is unknown. Here we address the role of IL-25 in skin fibrosis. Methods The expression of IL-25 was evaluated by immunofluorescence and in situ hybridization in 10 SSc and seven healthy donor (HD) skin biopsies. Epidermal equivalents (EE) reconstituted by primary HD keratinocytes were used as a model to study transcriptomic changes induced by IL-25 in the epidermis. RNA expression profile in EEs was characterized by RNAseq. The conditioned medium (CM) from primary SSc and HD keratinocytes primed with IL-25 was used to stimulate fibroblasts. IL-6, IL-8, MMP-1, type-I collagen (Col-I), and fibronectin production by fibroblasts was assessed by ELISA. Results SSc epidermis expressed lower levels of IL-25 compared with HDs. In EEs, IL-25 regulated several molecular pathways related to wound healing and extracellular matrix remodelling. Compared with control CM, the CM from IL-25-primed keratinocytes enhanced the fibroblast production of MMP-1, IL-6 and IL-8, but not of Col-I nor fibronectin. However, IL-25 significantly reduced the production of Col-I when applied directly to fibroblasts. The activation of keratinocytes by IL-25 was receptor-dependent and evident after a very short incubation time (10 min), largely mediated by IL-1, suggesting enhanced and specific release of preformed mediators. Conclusions These results show that IL-25 participates in skin homeostasis, and its decreased expression in SSc may contribute to skin fibrosis by favouring extracellular matrix deposition over degradation.
- Subjects :
- Keratinocytes
Epidermi
extra cellular matrix
Fibrosi
keratinocyte
fibroblast
IL-25
IL-17E
Rheumatology
Humans
scleroderma
Pharmacology (medical)
Fibronectin
Cells, Cultured
Skin
Scleroderma, Systemic
integumentary system
Interleukin-6
Interleukin-17
Interleukin-8
Fibroblasts
Fibrosis
Fibronectins
Culture Media, Conditioned
Epidermis
Matrix Metalloproteinase 1
systemic sclerosi
Human
Subjects
Details
- ISSN :
- 14620332
- Volume :
- 61
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Rheumatology (Oxford, England)
- Accession number :
- edsair.doi.dedup.....27e6d81bbc4dd8aa7954dab7eb2a8b25