Guy Dagregorio

A role for T cell-derived interleukin 22 in psoriatic skin inflammation.

Interleukin (IL)‐22 is a T cell‐derived cytokine that has been reported recently to induce cutaneous inflammation in an experimental murine model of psoriasis, and to induce in vitro an inflammatory‐like phenotype. In the present study, we assessed the presence of IL‐22 and the IL‐22 receptor 1 (IL‐22R1) in skin lesions, skin‐derived T cells, as well as IL‐22 levels in sera from patients with psoriasis. IL‐22R1 and IL‐10R2 transcripts are expressed at a similar level in psoriatic and healthy skin. In contrast, IL‐22 mRNA expression was up‐regulated in psoriatic skin lesions compared to normal skin, whereas IL‐22 mRNA levels in peripheral blood mononuclear cells from psoriatic patients and normal subjects were similar. Circulating IL‐22 levels were significantly higher in psoriatic patients than in normal subjects. T cells isolated from psoriatic skin produced higher levels of IL‐22 in comparison to peripheral T cells isolated from the same patients. IL‐10 was expressed at similar levels in skin biopsies and peripheral blood mononuclear cells of psoriatic patients and normal subjects. Finally, we show here that supernatants of lesional psoriatic skin‐infiltrating T cells induce an inflammatory response by normal human epidermal keratinocytes, resembling that observed in psoriatic lesions. Taken together, the results reported in this study indicate that IL‐22 is a cytokine produced by skin‐infiltrating lymphocytes that is potentially involved in initiation and/or maintenance of the pathogenesis of psoriasis.

Oncostatin M Secreted by Skin Infiltrating T Lymphocytes Is a Potent Keratinocyte Activator Involved in Skin Inflammation

Cutaneous inflammatory diseases such as psoriasis vulgaris and atopic dermatitis are associated with altered keratinocyte function, as well as with a particular cytokine production profile of skin-infiltrating T lymphocytes. In this study we show that normal human epidermal keratinocytes express a functional type II oncostatin-M (OSM) receptor (OSMR) consisting of the gp130 and OSMRβ components, but not the type I OSMR. The type II OSMR is expressed in skin lesions from both psoriatic patients and those with atopic dermatitis. Its ligand, OSM, induces via the recruitment of the STAT3 and MAP kinase pathways a gene expression profile in primary keratinocytes and in a reconstituted epidermis that is characteristic of proinflammatory and innate immune responses. Moreover, OSM is a potent stimulator of keratinocyte migration in vitro and increases the thickness of a reconstituted epidermis. OSM transcripts are enhanced in both psoriatic and atopic dermatitic skin as compared with healthy skin and mirror the enhanced production of OSM by T cells isolated from diseased lesions. Results from a microarray analysis comparing the gene-modulating effects of OSM with those of 33 different cytokines indicate that OSM is a potent keratinocyte activator similar to TNF-α, IL-1, IL-17, and IL-22 and that it acts in synergy with the latter cytokines in the induction of S100A7 and β-defensin 2 expression, characteristic of psoriatic skin. Taken together, these results demonstrate that OSM and its receptor play an important role in cutaneous inflammatory responses in general and that the specific effects of OSM are associated with distinct inflammatory diseases depending on the cytokine environment.

Bi‐acromial Dimples: A Series of Seven Cases

Abstract:  Seven patients with bi‐acromial dimples are reported, with a family history in only one. This skin condition presented as an anatomic peculiarity without associated abnormalities. Although it has been previously documented as a finding in malformation syndromes such as the 18q syndrome, we point out that it may be found quite frequently in isolation and without morbidity. Therefore, it should be mainly considered as an anatomic variation without pathologic significance.

Involvement of IL-1 and Oncostatin M in Acanthosis Associated With Hypertensive Leg Ulcer

Hypertensive leg ulcer (HLU) is an inflammatory disease characterized by intense pain, alteration of vascularization, and skin necrosis. The optimal treatment relies on surgical removal of necrotic tissues covered by a split-skin graft. We studied the histomorphology of the lesions and investigated the involvement of inflammatory cells and cytokines to further define the physiopathology of HLU. We report epidermis acanthosis and a preferential occlusion of the precapillary arterioles with infiltration of neutrophils, macrophages, and T lymphocytes in the dermis. OSM, IL-1β, and IL-6 were overexpressed in the ulcer, whereas the Th17-derived cytokines were not. In vitro, the addition of IL-1β and OSM promoted acanthosis and destructuring of reconstructed epidermis. Exogenous IL-1β and OSM synergistically induced epidermal acanthosis in mice. These data show that OSM and IL-1β are not only a biological characteristic signature of HLU, but these cytokines reflect a specific inflammatory state, directly involved in the pathogenesis. We suggest that anti-cytokine biotherapies could be an alternative strategy to surgery to treat HLU.

Vulvite d’hypersensibilité aux protéines séminales : 3 cas

Resume Introduction Le diagnostic etiologique d’une vulvite est parfois difficile, imposant de considerer toutes les possibilites de facteurs externes declencheurs ou aggravants. La vulvite post-coitale suggere plus electivement d’explorer une allergie seminale. Observations Trois observations d’allergie d’expression vulvaire sont rapportees : deux correspondaient a une hypersensibilite retardee au sperme de leur partenaire, avec patch test positif a 48 heures. Il n’y avait pas d’IgE specifiques anti-liquide seminal. La pertinence des tests cutanes etait confirmee par la chronologie des symptomes et par leur disparition lors des rapports proteges. La troisieme malade avait une vulvite oedemateuse avec urticaire, asthme et malaise lors des rapports sexuels : la positivite du prick test a lecture immediate et la presence d’IgE specifiques anti-proteines seminales permettait de poser le diagnostic d’allergie de type 1, confirme par la disparition de tous les symptomes vulvaires et generaux avec l’usage de preservatifs. Discussion La dermite de contact aux proteines seminales est susceptible de representer une etiologie meconnue de vulvite. Ces trois observations demontrent que cette piste merite d’etre exploree : les patch tests et les prick-tests representent un outil diagnostique capable de demontrer une allergie aux proteines seminales en cas de vulvite ou urticaire post-coitales.