Scientific article

IL-25 participates in keratinocyte-driven dermal matrix turnover and is reduced in systemic sclerosis epidermis

Published inRheumatology, keac044
Publication date2022-02-16
First online date2022-02-16

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.


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.


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.


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.

  • Epidermis
  • Extra cellular matrix
  • Fibroblast
  • Fibrosis
  • IL-17E
  • IL-25
  • Keratinocytes
  • Scleroderma
  • Skin
  • Systemic Sclerosis
Citation (ISO format)
RUSSO, Barbara et al. IL-25 participates in keratinocyte-driven dermal matrix turnover and is reduced in systemic sclerosis epidermis. In: Rheumatology, 2022, p. keac044. doi: 10.1093/rheumatology/keac044
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ISSN of the journal1462-0324

Technical informations

Creation09/13/2022 1:19:00 PM
First validation09/13/2022 1:19:00 PM
Update time03/16/2023 7:33:44 AM
Status update03/16/2023 7:33:43 AM
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