title: Serum autoantibodies in pristane induced lupus are regulated by neutrophil gelatinase associated lipocalin.
abstract: The onset of autoantibodies in systemic autoimmunity can be the result of a breakdown in tolerance at multiple checkpoints. Genetic, hormonal, and immunological factors can combine with environmental influences to accelerate the onset of disease and aggravate disease outcome. Here, we describe a novel mechanism relating to the regulatory role of Neutrophil Gelatinase Associated Lipocalin (NGAL) in modulating the levels of autoantibodies in pristane induced lupus. Following a single injection of pristane intraperitoneally, NGAL expression was induced in both the serum and spleen. Furthermore, NGAL deficient mice were more susceptible to the induction of pristane stimulated autoimmunity, and displayed higher numbers of autoantibody secreting cells and increased expression of activation induced cytidine deaminase (AID) and other inflammatory mediators in the spleen. In contrast, kidney damage was milder in NGAL deficient mice, indicating that NGAL was detrimental in autoantibody mediated kidney disease. These studies indicate that NGAL plays differential roles in different tissues in the context of lupus, and suggest a previously unrecognized role for NGAL in adaptive immunity.
authors: The Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Rahul D
authors: RD
authors: Pawar
authors: The Division of Pediatric Nephrology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Beatrice
authors: B
authors: Goilav
authors: The Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Yumin
authors: Y
authors: Xia
authors: The Division of Rheumatology & Clinical Immunology, University of Florida, Gainesville, FL 32611, USA.
authors: Haoyang
authors: H
authors: Zhuang
authors: The Department of Pathology, Columbia University Medical Center, NY 10032, USA.
authors: Leal
authors: L
authors: Herlitz
authors: The Division of Rheumatology & Clinical Immunology, University of Florida, Gainesville, FL 32611, USA.
authors: Westley H
authors: WH
authors: Reeves
authors: The Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: chaim.putterman@einstein.yu.edu.
authors: Chaim
authors: C
authors: Putterman
mesh_terms: D000209:Acute-Phase Proteins / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000097:blood; D007668:Kidney / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000276:immunology*; D013154:Spleen / Q000201:enzymology / Q000378:metabolism; D013729:Terpenes
chemical_list: D000209:Acute-Phase Proteins; D001323:Autoantibodies; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D013729:Terpenes; D018664:Interleukin-12; C009042:pristane
keywords: Autoantibodies; Lipocalin-2; NGAL; Pristane; SLE