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SFB 1192

Projekt A7

Neutrophil extracellular traps in lupus nephritis

Neutrophils release extracellular traps (NETs) during sterile inflammation and infection. NETs are lattices of intact chromatin filaments that are decorated with biologically active proteins and peptides. In autoimmune diseases, NETs provide a substrate for autoantibodies and the formation of pathological immune complexes. Recently, we could show that two host DNases, DNASE1 and DNASE1-LIKE 3 (DNASE1L3), degrade intravascular NETs. Mutations in DNASE1 and DNASE1L3 have been identified in systemic lupus erythematosus (SLE) patients. Defective NET degradation has been associated with a poor prognosis for developing lupus nephritis (LN). Here, we hypothesize that a deficiency in host DNases generates incompletely digested NETs, which sequester autoantibodies and thus drive the deposition of pathogenic immune complexes in LN. To test our hypothesis, we will analyse NET formation in murine LN and study genetic or acquired deficiencies that cause impaired NET degradation.

Publikationen

  • 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


Projekt-Team

Projektleiter:
Dr. Tobias Fuchs

Mitarbeiter:
Dr. Mylène Divivier
Josephine Göbel