Journal
LANCET
Volume 382, Issue 9894, Pages 819-831Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0140-6736(13)60954-X
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Funding
- DFG CRC initiative [(SFB) 633, (SFB) 650]
- DFG [Do491/8-1, Do491/8-2, Do491/8-7, Do491/8-3]
- SPP Immunobone
- Swedish Research Council
- Swedish Rheumatism Association
- Swedish Heart Lung Foundation
- King Gustaf Vth 80-year Foundation
- Soderberg Foundation
- Karolinska Institute
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Systemic lupus erythematosus, Sjogren's syndrome, and dermatomyositis are systemic autoimmune diseases that develop after environmental triggering of genetically susceptible individuals. The precise cellular and molecular mechanisms leading to autoimmune disease, and what factors determine which organs are involved, remain poorly understood. Recent insights into genetic susceptibility now make obvious that environmental triggers often act via cellular pathways containing disease-associated polymorphisms. In the breaking of tolerance, the initiating tissue-including dendritic cells-provides a decisive microenvironment that affects immune-cell differentiation, leading to activation of adaptive immunity. Type 1 interferon produced by innate immune cells has a central role in systemic autoimmunity and activates B cells and T cells. In turn, B-cell-derived autoantibodies stimulate dendritic cells to produce type 1 interferon; thus, a positive feedforward loop is formed that includes both the innate and adaptive systems. New treatments could simultaneously and specifically target several such vital pathways in autoimmunity.
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