Phospholipase activity of acyloxyacyl hydrolase induces IL‐22‐producing CD1a‐autoreactive T cells in individuals with psoriasis
Randeep Singh, Yi‐Ling Chen, Soo Weei Ng, David Cain, Rachel Etherington, Clare S. Hardman, Graham S. Ogg
Abstract
Abstract Psoriasis is a chronic inflammatory skin disease characterized by Th17 responses. Recent evidence has identified Langerhans cells to have a key role in disease pathogenesis, with constitutive high expression of CD1a and capacity to present lipid antigens to T cells. Phospholipase A 2 enzymes generate neolipid antigens for recognition by CD1a‐reactive T cells; however, the broader enzymatic pathways of CD1a lipid ligand generation have not been thoroughly investigated. In this study, we used immunofluorescence of skin and ELISpot analyses of CD1a‐reactive T cells to investigate the role of the lipase acyloxyacyl hydrolase (AOAH) in CD1a ligand generation with relevance to the pathogenesis of psoriasis. We found that the PLA 2 activity of rAOAH leads to the activation of circulating CD1a auto‐reactive T cells, leading to the production of IFN‐γ and IL‐22. Circulating AOAH‐responsive CD1a‐reactive T cells from patients with psoriasis showed elevated IL‐22 production. We observed that AOAH is highly expressed in psoriatic lesions compared to healthy skin. Overall, these data present a role for AOAH in generating antigens that activate circulating lipid‐specific CD1a‐restricted T cells and, thus, contribute to psoriatic inflammation. These findings suggest that inhibition of PLA 2 activity of AOAH may have therapeutic potential for individuals with psoriasis.