No abstract

Background Atopic dermatitis (AD) and psoriasis represent two of the most common inflammatory skin diseases in developed countries. A hallmark of both diseases is T‐cell infiltration into the skin. However, it is still not clarified to what extent these infiltrating T cells are antigen‐specific skin‐homing T cells or unspecific heterogeneous bystander cells. Methods To elucidate this, T cells from lesional skin and from blood of 9 AD and 10 psoriasis patients were compared by receptor (TCR) sequencing. Therefore, peripheral blood mononuclear cells (PBMC) were cell‐sorted according to expression of the cutaneous leukocyte antigen (CLA) into skin‐homing (CLA+) and non‐skin‐homing (CLA−) subfractions. Aeroallergen‐specific T‐cell lines were grown from AD patients’ PBMC in parallel. Results Intra‐individual comparison of TCRB CDR3 regions revealed that clonally expanded T cells in skin lesions of both AD and psoriasis patients corresponded to skin‐homing circulating T cells. However, in psoriasis patients, these T‐cell clones were also detectable to a larger extent among CLA− circulating T cells. Up to 28% of infiltrating cells in AD skin were identified as allergen‐specific by overlapping TCR sequences. Conclusions Our data show that in line with the systemic nature of psoriasis, T‐cell clones that infiltrate psoriatic skin lesions do not exclusively possess skin‐homing ability and are therefore most probably specific to antigens that are not exclusively expressed or located in the skin. T cells driving AD skin inflammation appear to home nearly exclusively to the skin and are, to a certain extent, specific to aeroallergens.

Atopic dermatitis (AD) and psoriasis represent two of the most common inflammatory skin diseases in developed countries. A hallmark of both diseases is T cell infiltration into the skin. However, it is still not clarified to what extent these infiltrating T cells are antigen-specific skin-homing T cells or unspecific heterogeneous bystander cells. To elucidate this, T cells from lesional skin and from blood of 10 AD and 11 psoriasis patients were compared by receptor (TCR) sequencing. Therefore, peripheral blood mononuclear cells (PBMC) were cell-sorted according to expression of the cutaneous leukocyte antigen (CLA) into skin-homing (CLA+) and non-skin-homing (CLA-) subfractions. Aeroallergen-specific T cell lines were grown from AD patients' PBMC in parallel. Intra-individual comparison of TCRB CDR3 regions revealed that clonally expanded T cells in skin lesions of both AD and psoriasis patients corresponded to skin-homing circulating T cells. However, in psoriasis patients, these T cell clones were also detectable to a larger extent among CLA- circulating T cells. Up to 28% of infiltrating cells were identified as allergen-specific by overlapping TCR sequences. Our data shows that in line with the systemic nature of psoriasis, T cells infiltrating psoriatic skin lesions do not exclusively home to the skin and are therefore not specific to antigens that are exclusively encountered at the skin. T cells driving AD skin inflammation appear to home nearly exclusively to the skin and are, to a certain extent, specific to aeroallergens.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by skin barrier defects and a misdirected type 2 immune response against antigens. The skin microbiome in AD is characterised by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis (S. epidermidis). To assess whether S. epidermidis antigens play a role in AD, we studied the immune response against the extracellular serine protease (Esp). Methods: We analyzed the binding of human IgG4 to S. epidermidis extracellular proteins using immunoblotting and mass spectrometry. We then measured serum antibodies specific for recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry. Results: We identified Esp as the dominant IgG4-binding antigen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. The T cell response to Esp in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients’ T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33. Conclusions: Esp elicits type 2-biased response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.