Format

Send to

Choose Destination
See comment in PubMed Commons below
Lancet. 2013 Aug 31;382(9894):819-31. doi: 10.1016/S0140-6736(13)60954-X.

Immunopathogenic mechanisms of systemic autoimmune disease.

Author information

1
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Abstract

Systemic lupus erythematosus, Sjögren'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.

PMID:
23993191
DOI:
10.1016/S0140-6736(13)60954-X
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center