005 Cell-specific, disease-associated and variant-linked alterations in expression of ERAP1, ERAP2 And LNPEP aminopeptidases

ERAP1, ERAP2 and LNPEP are aminopeptidases implicated in autoimmune pathophysiology. Here, we demonstrate that is upregulated ERAP1 downregulated patients with psoriasis who homozygous for autoimmune-linked variants of ERAP. We also aminopeptidase expression not uniform the skin. Specifically, intracellular antigen-processing were strongly expressed basal early spinous layer keratinocytes, while granular keratinocytes predominantly LNPEP, an specialized processing extracellular antigens MHC class I cross-presentation. In psoriasis, T-cell monocyte-attracting chemokine, CCL2, supporting cytokine, IL-15. contrast, TGF-b1 was major cytokine by healthy control keratinocytes. SFRP2-high dermal fibroblasts noted to have ERAP2-high phenotype elevated HLA-C. fibroblast subpopulation CXCL14. From these results, postulate 1) increased ERAP2/ERAP1 ratio results altered antigen processing, a potential mechanism which ERAP risk alleles predispose individuals autoimmunity; 2) expressing cells display unique MHC-bound peptidome, generated from antigens; 3) peptidome skewed toward antigens.