Search

Background: Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL‐17C is an epithelial‐derived cytokine, whose impact on skin inflammation is unclear. Objective: We sought to characterize the role of IL‐17C in human ISD. Methods: IL‐17C gene and protein expression was assessed by immunohistochemistry and transcriptome analysis. Primary human keratinocytes were stimulated and expression of cytokines chemokines was determined by qRT‐PCR and luminex assay. Neutrophil migration towards supernatant of stimulated keratinocytes was assessed. IL‐17C was depleted using a new IL‐17C‐specific antibody (MOR106) in murine models of psoriasis (IL‐23 injection model) and AE (MC903 model) as well as in human skin biopsies of psoriasis and AE. Effects on cell influx (mouse models) and gene expression (human explant cultures) were determined. Results: Expression of IL‐17C mRNA and protein was elevated in various ISD. We demonstrate that IL‐17C potentiates the expression of innate cytokines, antimicrobial peptides (IL‐36G, S100A7 and HBD2) and chemokines (CXCL8, CXCL10, CCL5 and VEGF) and the autocrine induction of IL‐17C in keratinocytes. Cell‐free supernatant of keratinocytes stimulated with IL‐17C was strongly chemotactic for neutrophils, thus demonstrating a critical role for IL‐17C in immune cell recruitment. IL‐17C depletion significantly reduced cell numbers of T cells, neutrophils and eosinophils in murine models of psoriasis and AE and led to a significant downregulation of inflammatory mediators in human skin biopsies of psoriasis and AE ex vivo. Conclusion: IL‐17C amplifies epithelial inflammation in Th2 and Th17 dominated skin inflammation and represents a promising target for the treatment of ISD. [ABSTRACT FROM AUTHOR]

Background: Imbalances of T‐cell subsets are hallmarks of disease‐specific inflammation in psoriasis. However, the relevance of B cells for psoriasis remains poorly investigated. Objective: To analyse the role of B cells and immunoglobulins for the disease‐specific immunology of psoriasis. Methods: We characterized B‐cell subsets and immunoglobulin levels in untreated psoriasis patients (n = 37) and compared them to healthy controls (n = 20) as well as to psoriasis patients under disease‐controlling systemic treatment (n = 28). B‐cell subsets were analysed following the flow cytometric gating strategy based on the surface markers CD24, CD38 and CD138. Moreover, immunofluorescence stainings were used to detect IgA in psoriatic skin. Results: We found significantly increased levels of IgA in the serum of treatment‐naïve psoriasis patients correlating with disease score. However, IgA was only observed in dermal vessels of skin sections. Concerning B‐cell subsets, we only found a moderately positive correlation of CD138+ plasma cells with IgA levels and disease score in treatment‐naïve psoriasis patients. Confirming our hypothesis that psoriasis can develop in the absence of functional humoral immunity, we investigated a patient who suffered concomitantly from both psoriasis and a hereditary common variable immune defect (CVID) characterized by a lack of B cells and immunoglobulins. We detected variants in three of the 13 described genes of CVID and a so far undescribed variant in the ligand of the TNFRSF13B receptor leading to disturbed B‐cell maturation and antibody production. However, this patient showed typical psoriasis regarding clinical presentation, histology or T‐cell infiltrate. Finally, in a group of psoriasis patients under systemic treatment, neither did IgA levels drop nor did plasma cells correlate with IgA levels and disease score. Conclusion: B‐cell alterations might rather be an epiphenomenal finding in psoriasis with a clear dominance of T cells over shifts in B‐cell subsets. [ABSTRACT FROM AUTHOR]

B Is the humoral immunity dispensable for the pathogenesis of psoriasis? This corrigendum is to note that the name of Prof. Carsten Schmidt-Weber was inadvertently omitted as an author in the initial version of the paper. [Extracted from the article]