SFB 1192

Project A7

The Role of Neutrophil Extracellular Traps in Lupus Nephritis

Neutrophil Extracellular Traps (NETs) are lattices of extracellular DNA fibers decorated with histones and enzymes from neutrophil granules. NETs are released by neutrophils during infection and thrombosis, where they immobilize bacteria and provide scaffolding for blood clotting, respectively. NETs are also linked to several autoimmune diseases, including systemic lupus erythematosus (SLE). The association of NETs with SLE is ambivalent. In vitro, NETs are targeted by autoantibodies and stimulate the adaptive immunity, indicating a vicious circle of NET-formation and autoimmunity. However the role of NETs in SLE in vivo is not clearly understood.

The new project A7 addresses the role of NETs in lupus nephritis in murine models and in patients with 4 specific aims:

  1. Role of NETs in the induction of autoimmunity in murine lupus nephritis
  2. Role of NET-immune complexes in lupus nephritis
  3. Cloning of anti-NETantibodies
  4. Diagnostic value of NETs in patients with immune-mediated glomerulonephritis (GN).

Taking together, the proposed studies will improve the understanding of the interplay of NETs and autoimmunity and may set the groundwork for new diagnostic and therapeutic strategies for patients with lupus nephritis.

Neutrophil Extracellular Traps (NETs). (A) Electron micrograph of bacteria entangled in NETs. Image courtesy of Dr. Volker Brinkmann. Reproduced from Fuchs et al. [1]. (B) Scheme of hallmarks of NET-formation (NETosis). (C) Scheme of antimicrobial, prothrombotic, cytotoxic, and immunogenic NET functions..

Publications

  • Host DNases prevent vascular occlusion by neutrophil extracellular traps.

    Jiménez-Alcázar M, Rangaswamy C, Panda R, Bitterling J, Simsek YJ, Long AT, Bilyy R, Krenn V, Renné C, Renné T, Kluge S, Panzer U, Mizuta R, Mannherz HG, Kitamura D, Herrmann M, Napirei M, Fuchs TAScience. 2017 Dec

III. Medizinische Klinik und Poliklinik
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