PD-1 immunobiology in systemic lupus erythematosus

• Type of Material: Article
• Authors: Colleen S. Curran, National Institutes of Health; Sarthak Gupta, National Institute of Arthritis and Musculoskeletal and Skin Diseases; Ignacio Sanz, Emory University; Elad Sharon, National Cancer Institute
• Language: English
• Date: 2019-02-01
• Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jaut.2018.10.025
• Title of Journal or Parent Work: JOURNAL OF AUTOIMMUNITY
• Volume: 97
• Start Page: 1
• End Page: 9
• Grant/Funding Information: National Institutes of Health, Intramural Research Funds.
• Keywords: NON-HODGKIN-LYMPHOMA; DISEASE-ACTIVITY; Science & Technology; ARYL-HYDROCARBON RECEPTOR; Epstein-Barr virus; SIGNALING PATHWAY; NF-KAPPA-B; Life Sciences & Biomedicine; Immunology; Aryl hydrocarbon receptor; PD-1; REGULATORY T-CELLS; EPSTEIN-BARR-VIRUS; DEATH 1 POLYMORPHISMS; CHRONIC LYMPHOCYTIC-LEUKEMIA; Systemic lupus erythematosus; TOLL-LIKE RECEPTORS
• Research Categories: Health Sciences, Immunology; Biology, Cell; Biology, Virology

Abstract

Programmed death (PD)-1 receptors and their ligands have been identified in the pathogenesis and development of systemic lupus erythematosus (SLE). Two key pathways, toll-like receptor and type I interferon, are significant to SLE pathogenesis and modulate the expression of PD-1 and the ligands (PD-L1, PD-L2) through activation of NF-κB and/or STAT1. These cell signals are regulated by tyrosine kinase (Tyro, Axl, Mer) receptors (TAMs) that are aberrantly activated in SLE. STAT1 and NF-κB also exhibit crosstalk with the aryl hydrocarbon receptor (AHR). Ligands to AHR are identified in SLE etiology and pathogenesis. These ligands also regulate the activity of the Epstein-Barr virus (EBV), which is an identified factor in SLE and PD-1 immunobiology. AHR is important in the maintenance of immune tolerance and the development of distinct immune subsets, highlighting a potential role of AHR in PD-1 immunobiology. Understanding the functions of AHR ligands as well as AHR crosstalk with STAT1, NF-κB, and EBV may provide insight into disease development, the PD-1 axis and immunotherapies that target PD-1 and its ligand, PD-L1.