Lupus Casts a Complicated NET

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Science  25 Mar 2011:
Vol. 331, Issue 6024, pp. 1493
DOI: 10.1126/science.331.6024.1493-c

Systemic lupus erthymatosis is a debilitating autoimmune disease that is characterized by the accumulation of inflammatory immune complexes (antibodies bound to a person's own nuclear structures) in tissues. Lupus patients exhibit alterations in cytokine production and in various immune cell numbers and functions, but how these changes contribute to disease pathogenesis is not well understood. Lande et al. and Garcia-Romo et al. analyze serum samples and cells isolated from lupus patients and report that immune complexes, type I interferons, and neutrophils are entwined in a vicious cycle that drives disease pathogenesis. This trio of immune mediators is elevated in lupus serum, and together they induce a type of cell death in neutrophils called NETosis, where neutrophils spew out their nuclear contents (NETs). NETs drive further production of interferons, which in turn induces more NETosis. NETs are also an antigenic source for the generation of more immune complexes. With only one targeted therapy available for lupus, new therapeutic targets such as these are badly needed.

Sci. Transl. Med. 3, 73ra19; 73ra20 (2011).

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