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

• Published in: Allergy (Copenhagen) 2022-09, Vol.77 (9), p.2737-2747
• Main Authors: Roesner, Lennart M., Farag, Ahmed K., Pospich, Rebecca, Traidl, Stephan, Werfel, Thomas
• Format: Article
• Language: English
• Subjects: allergen; Allergens; Antigens; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; Atopic dermatitis; Cell lines; clone; Complementarity-determining region 3; Dermatitis; Dermatitis, Atopic; Eczema; Homing behavior; Humans; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Lymphocytes; Lymphocytes T; Membrane Glycoproteins; Peripheral blood mononuclear cells; Psoriasis; Receptors, Antigen, T-Cell - genetics; Receptors, Lymphocyte Homing; skin; Skin diseases; Skin lesions; T cell; T cell receptors
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.15272

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. T cell repertoires of lesional skin of atopic dermatitis (AD) and psoriasis are mirrored predominantly by circulating CLA+ T cells. Highly clonally propagated T cells in AD lesional skin are largely derived from circulating CLA+ T cells, in contrast to psoriasis. Aeroallergen‐specific T cells are part of the AD skin infiltrate.Abbreviations: AD, atopic dermatitis; CLA, cutaneous leukocyte antigen; TCR, T cell receptor