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.
Background Atopic dermatitis (AD) is one of the most common inflammatory skin diseases worldwide and Staphylococcus aureus colonization and secondary infections occur in the majority of AD patients. Allergic sensitizations against microbial antigens have been discussed as possible trigger factors of AD. Recently, we reported IgE sensitization against fibronectin‐binding protein 1 (FBP1), an essential virulence component in S. aureus, in a subgroup of patients suffering from AD. To expand these findings by investigating delayed‐type immune reactions, the objective of this study was to detect and phenotypically characterize FBP1‐specific T cells as possible trigger factors in AD. Methods Immunodominant T‐cell epitopes were mapped by proliferation testing of patient‐derived FBP1‐specific T‐cell lines after stimulation with single 15mer peptides, which were derived from different functional domains of the FBP1 sequence. Major histocompatibility complex class II tetramers carrying immunodominant epitopes successfully stained T helper cells in 8 out of 8 HLA‐matched, IgE‐sensitized AD patients. Results Cytokine profiling of multimer‐sorted cells revealed that predominantly the type 2 cytokines IL‐13 and IL‐4 were secreted by these cells. In contrast, IL‐17, the marker cytokine for response to extracellular pathogens, was scarcely detectable. Conclusions We demonstrate that FBP1 contains immunodominant peptides that induce a specific pro‐inflammatory T helper cell response with increased Th2 levels that can drive an allergic inflammation in sensitized AD patients.
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.
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