Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a

Abstract

In psoriasis, IFN-α–stimulated mast cells release exosomes containing cytoplasmic PLA2 that are transferred to CD1a-expressing cells and generate neolipid antigens which induce the production of IL-22 and IL-17A by CD1a-reactive T cells.

Clinically resolved psoriatic lesions contain psoriasis-specific IL-17–producing αβ T cell clones

“…Deidentified samples of biopsy-proven eczematous derSeveral putative antigens have been identified in psoriasis. Two-thirds of patients with psoriasis have T cells reactive to LL37 (16), and neolipid antigens were recognized by a subset of CD1a-restricted T cells in psoriatic skin lesions (17,18). Reactivity to the melanocyte antigen ADAMTSL5 was observed in CD8 + T cells from psoriasis patients, but not healthy controls (7), although patients with psoriasis do not generally develop vitiligo, a sequelae of autoimmune targeting of melanocytes.…”

Psoriasis: a mixed autoimmune and autoinflammatory disease

“…Frequency of both CD1b[20] and CD1a[21] autocreactive T cells is found to increase in psoriasis patients compared to healthy controls. Several phospholipases, including PLA2G4D and PLA2G2F, are increased in psoriatic skin[21,22], but these enzymes play a role in generation of phospholipid neoantigens. No genetic variants in psoriasis have been associated with lipid processing or presentation.…”

A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease

“…+ DCs, it might even mediate the presentation of lipids onto nonclassical MHC class I and the priming of CD1a-restricted Th22, as seen in patients with psoriasis (14,43).…”