Immunopathogenic mechanisms of systemic autoimmune disease

Lancet. 2013 Aug 31;382(9894):819-31. doi: 10.1016/S0140-6736(13)60954-X.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age of Onset
  • Autoimmune Diseases / etiology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Autoimmunity / immunology
  • B-Lymphocytes / immunology
  • Cytokines / immunology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Interferons / immunology
  • Major Histocompatibility Complex / immunology
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Cytokines
  • Interferons