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.
T cell receptor sequencing specifies psoriasis as a systemic and atopic dermatitis as a skin-focused, allergen-driven disease