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

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

Is neutrophilic dermatosis a manifestation of familial Mediterranean fever?

International audienceObjectives: Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease. It is associated with MEFV mutations. Its main features are recurrent episodes of fever and serositis. Patients can display dermatological manifestations such as erysipelas-like erythema, generally considered as a neutrophilic dermatosis (ND). It has been suggested that FMF can be associated with other types of ND. Our aim was to perform a systematic review of the literature to assess the link between ND and FMF.Method: A systematic review of the literature was performed using MEDLINE from 1946 to 2018. Three independent investigators identified reports of non-erysipelas-like erythema neutrophilic dermatosis (NEND) associated with FMF, selected the criteria to establish the diagnosis of FMF and ND, and evaluated the link between the two conditions. FMF-associated NEND was supported by confirmation of both diagnoses and exclusion of other causes of ND.Results: Eighteen articles were selected. Nine articles reported FMF patients with the following NEND: neutrophilic panniculitis (n = 4), Sweet syndrome (n = 6), and pyoderma gangrenosum (n = 1). None of these cases was supported by histological confirmation, fulfilled diagnostic criteria for definitive or probable FMF, or confirmed the exclusion of all the most frequent diseases associated with NEND. As a result, there is insufficient evidence to support a potential relationship between NEND and FMF.Conclusions: The association between FMF and NEND remains unclear. In FMF patients with NEND, every differential diagnosis and alternative cause of NEND should be excluded before drawing any conclusions about a potential causal relationship

Lichen plan buccal erosif associe a un syndrome de Good [Oral erosive lichen planus associated with Good syndrome]

Introduction. - Good syndrome is characterized by thymoma, hypogammaglobulinemia, low number of peripheral B cells, and variably, peripheral CD4 T cell lymphopenia and inverted CD4/CD8 T cell ratio, associated with infections and autoimmune diseases