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

Allergy. 2022 Sep;77(9):2737-2747. doi: 10.1111/all.15272. Epub 2022 Mar 14.

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.

Keywords: T cell; allergen; atopic dermatitis; clone; skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Neoplasm
  • Dermatitis, Atopic*
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Membrane Glycoproteins
  • Psoriasis*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Lymphocyte Homing

Substances

  • Allergens
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Neoplasm
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell
  • Receptors, Lymphocyte Homing