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

Moguelet, Philippe
Truchetet, Marie-Elise
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Published in Rheumatology. 2022, keac044
Abstract 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.

Keywords EpidermisExtra cellular matrixFibroblastFibrosisIL-17EIL-25KeratinocytesSclerodermaSkinSystemic Sclerosis
PMID: 35171244
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Research groups Développement du système hémato-vasculaire chez les vertébrés (920)
Mécanismes des pathologies de l'inflammation cutanée (919)
Swiss National Science Foundation: 310030_159999
Swiss National Science Foundation: 310030_152680
Swiss National Science Foundation: 310030_175470
Swiss National Science Foundation: 310030_184814
(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 https://archive-ouverte.unige.ch/unige:163379

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Deposited on : 2022-09-20

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