The following is a summary of “Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis,” published in the July 2023 issue of Investigative Dermatology by Marusina et al.
Aminopeptidases ERAP1, ERAP2, and LNPEP are involved in autoimmune pathophysiology. This study demonstrates that ERAP2 is upregulated and ERAP1 is downregulated in psoriasis patients homozygous for ERAP variants associated with autoimmunity. In addition, the researchers show that aminopeptidase expression in the epidermis is not uniform. In particular, the intracellular antigen-processing aminopeptidases ERAP1 and ERAP2 are highly expressed in basal and early spinous layer keratinocytes.
In contrast, granular layer keratinocytes express primarily LNPEP, an aminopeptidase specializing in processing extracellular antigens for presentation to T cells. In psoriasis, basal keratinocytes also expressed CCL2, a chemokine that attracts T cells and monocytes, and IL-15, a cytokine that supports T cells. In contrast, the predominant cytokine expressed by healthy basal keratinocytes was TGF-1. SFRP2-high dermal fibroblasts were also found to express ERAP2-high and HLA-C at elevated levels.
In psoriasis, the fibroblast subpopulation characterized by a high level of SFRP2 also exhibited elevated levels of CXCL14. They hypothesize that an increased ERAP2/ERAP1 ratio results in altered antigen processing, a potential mechanism by which ERAP risk alleles predispose individuals to autoimmunity; ERAP2-high expressing cells display a distinct major histocompatibility complex–bound peptidome generated from intracellular antigens; and the granular layer peptidome is skewed toward extracellular antigens.