Regulation of lupus nephritis by NCR+ innate lymphoid cells and type III interferons

Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease mostly affecting women of childbearing age. One of the main factors of morbidity and reduced life expectancy is renal disease due to several different entities of glomerulonephritis and glomerular injury, ranging from mild inflammation to irreversible loss of renal function requiring dialysis. Several lines of evidence suggest an implication of NK cells in the course of disease, but it is still controversial whether they play a protective or rather a detrimental role. Innate lymphoid cells (ILC) have been extensively studied in various tissues such as lung and gut but so far their presence and role in the kidney has only been poorly investigated. In this study, we found that homeostatic kidneys harbor conventional NK cells, ILC1, ILC2 and ILC3 and studied the role of NKp46+NK1.1+ (NCR+) ILC in murine models of lupus nephritis. It is widely accepted that type I interferons play a significant role in the pathogenesis of human SLE and NZB/W F1 mice treated with poly(I:C), a synthetic dsRNA mimic which induces a type I IFN response, develop an accelerated and aggressive form of glomerulonephritis with high prevalence of epithelial proliferative lesions (crescents), predictors of rapidly fatal disease in humans. NCR+ ILC increased in numbers in the course of poly(I:C)-induced disease and showed signs of activation, proliferation and cytokine production. In vivo depletion of NCR+ ILC by anti-NK1.1 or anti-asialoGM1 led to a clear amelioration of disease with reduced proteinuria, crescent formation, kidney inflammation and mice with reduced numbers of NCR+ ILC or treated with anti-IFNγ showed reduced numbers of F4/80hi macrophages previously shown to play a pivotal role in end-organ damage. Numbers of dsDNA-specific ASCs were reduced in the kidneys, unaffected in the spleen and even increased in the bone marrow of NZB/W F1 mice depleted from NCR+ ILC, possibly pointing to a differential role of the latter in the kidney (promoting inflammation) and periphery (restricting autoimmunity). Lastly, we identified a role for type III interferons in the generation of autoantibodies and homing of kidney antibody secreting-cells in pristane-induced lupus

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Universität Freiburg, Dissertation, 2016

Classification and Topics

• Keyword: Autoaggressionskrankheit ; Tiermodell ; Systemischer Lupus erythematodes ; Immunologe

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2023
• Creator: Aschman, Tom
• Contributor: Voll, Reinhard ; Voll, Reinhard ; Prinz, Marco ; Klinik für Rheumatologie und Klinische Immunologie. Freiburg im Breisgau ; Universitätsklinikum Freiburg. Department für Medizinische Mikrobiologie und Hygiene ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät

Further information

• DOI: 10.6094/UNIFR/236518
• URN: urn:nbn:de:bsz:25-freidok-2365180
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:49 PM CET