TLR recognition of self nucleic acids hampers.pdfVIP

Vol 465 | 17 June 2010 | doi:10.1038/nature09102 LETTERS TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus 1 1 2 2 2 1 1 Cristiana Guiducci , Mei Gong , Zhaohui Xu , Michelle Gill {, Damien Chaussabel , Thea Meeker , Jean H. Chan , 3,4 3,4 5 6 2 1 Tracey Wright , Marilynn Punaro , Silvia Bolland , Vassili Soumelis , Jacques Banchereau , Robert L. Coffman , Virginia Pascual2,3 Franck J. Barrat1 Glucocorticoids are widely used to treat patients with auto- administered orally on a daily basis, as the typical every other day immune diseases such as systemic lupus erythematosus (SLE)1,2. regimens cannot maintain disease control. When doses greater than However, regimens used to treat many such conditions cannot 40 mg per day are required, patients receive intravenous methylpred- maintain disease control in the majority of SLE patients and more nisolone (Solu-Medrol) pulse therapy (30 mg kg21 up to 1 g day21). aggressive approaches such as high-dose methylprednisolone Such treatment can transiently reduce disease activity, but often does pulse therapy are used to provide transient reductions in disease not induce remission or prevent end organ damage2–4. The reason activity3,4. The primary anti-inflammatory mechanism of gluco- why treatment of SLE requires much higher glucocorticoid doses corticoids is thought to be NF-kB inhibition5. Recognition of self