دورية أكاديمية
Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis.
| العنوان: | Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis. |
|---|---|
| المؤلفون: | Marusina AI; Department of Dermatology, University of California, Davis, Sacramento, California, USA., Ji-Xu A; Department of Dermatology, University of California, Davis, Sacramento, California, USA., Le ST; Department of Dermatology, University of California, Davis, Sacramento, California, USA., Toussi A; Department of Dermatology, University of California, Davis, Sacramento, California, USA., Tsoi LC; Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA., Li Q; Department of Dermatology, University of California, Davis, Sacramento, California, USA., Luxardi G; Department of Dermatology, University of California, Davis, Sacramento, California, USA., Nava J; Department of Dermatology, University of California, Davis, Sacramento, California, USA., Downing L; Department of Dermatology, University of California, Davis, Sacramento, California, USA., Leal AR; Department of Dermatology, University of California, Davis, Sacramento, California, USA., Kuzminykh NY; Institute of Biochemical Physics, Russian Academy of Science, Moscow, Russia., Kruglinskaya O; Physioseq LLC, Sacramento, California, USA., Brüggen MC; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Swiss Institute for Allergy Research, Davos, Switzerland., Adamopoulos IE; Division of Rheumatology and Clinical Immunology, Harvard Medical School, Beth Israel Medical Deaconess Center, Boston, Massachusetts, USA., Merleev AA; Department of Dermatology, University of California, Davis, Sacramento, California, USA., Gudjonsson JE; Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA., Maverakis E; Department of Dermatology, University of California, Davis, Sacramento, California, USA. Electronic address: emaverakis@ucdavis.edu. |
| المصدر: | The Journal of investigative dermatology [J Invest Dermatol] 2023 Jul; Vol. 143 (7), pp. 1157-1167.e10. Date of Electronic Publication: 2023 Jan 28. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 0426720 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-1747 (Electronic) Linking ISSN: 0022202X NLM ISO Abbreviation: J Invest Dermatol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2016- : New York : Elsevier Original Publication: Baltimore, Williams & Wilkins. |
| مواضيع طبية MeSH: | Genetic Predisposition to Disease* , Psoriasis*/genetics, Humans ; Aminopeptidases/genetics ; Phenotype ; Cytokines/genetics ; Minor Histocompatibility Antigens/genetics ; Polymorphism, Single Nucleotide |
| مستخلص: | ERAP1, ERAP2, and LNPEP are aminopeptidases implicated in autoimmune pathophysiology. In this study, we show that ERAP2 is upregulated and ERAP1 is downregulated in patients with psoriasis who are homozygous for autoimmune-linked variants of ERAP. We also demonstrate that aminopeptidase expression is not uniform in the skin. Specifically, the intracellular antigen-processing aminopeptidases ERAP1 and ERAP2 are strongly expressed in basal and early spinous layer keratinocytes, whereas granular layer keratinocytes expressed predominantly LNPEP, an aminopeptidase specialized in the processing of extracellular antigens for presentation to T cells. In psoriasis, basal keratinocytes also expressed the T-cell- and monocyte-attracting chemokine, CCL2, and the T-cell-supporting cytokine, IL-15. In contrast, TGF-β1 was the major cytokine expressed by healthy control basal keratinocytes. SFRP2-high dermal fibroblasts were also noted to have an ERAP2-high expression phenotype and elevated HLA-C. In psoriasis, the SFRP2-high fibroblast subpopulation also expressed elevated CXCL14. From these results, we postulate that (i) an increased ERAP2/ERAP1 ratio results in altered antigen processing, a potential mechanism by which ERAP risk alleles predispose individuals to autoimmunity; (ii) ERAP2-high expressing cells display a unique major histocompatibility complex-bound peptidome generated from intracellular antigens; and (iii) the granular layer peptidome is skewed toward extracellular antigens. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
| المشرفين على المادة: | EC 3.4.11.- (Aminopeptidases) 0 (Cytokines) 0 (Minor Histocompatibility Antigens) EC 3.4.11.- (ERAP1 protein, human) EC 3.4.11.- (ERAP2 protein, human) |
| تواريخ الأحداث: | Date Created: 20230130 Date Completed: 20230626 Latest Revision: 20240108 |
| رمز التحديث: | 20240108 |
| DOI: | 10.1016/j.jid.2023.01.012 |
| PMID: | 36716917 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1523-1747 |
|---|---|
| DOI: | 10.1016/j.jid.2023.01.012 |