Biomedicine Select

  • Published 2007 in Cell


Autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, are complex disorders characterized by an inflammatory response against the body's own tissues. Recent findings reveal new insights into how these diseases are initiated and progress and the factors that contribute to their clinical symptoms. Such work also pinpoints potential new therapeutic targets including the integrated stress response, cadherins, and Wnt signaling. Mast cells of the immune system are on the frontline in the war against bacterial and parasitic invaders. Despite their commendable efforts, when mast cells get trigger-happy—attacking both friend and foe alike—autoimmune disorders or allergy may be the result. The dark tendencies latent in mast cells are further explored by Nigrovic et al. (2007) using a mouse model in which inflammatory arthritis is induced by the presence of autoreactive antibodies. In previous work, animals lacking mast cells were found to be resistant to this type of experimental arthritis. Nigrovic et al. now provide evidence that mast cells are directly activated by immune complexes containing these autoantibodies, resulting in their production of the inflammatory cytokine interleukin-1 (IL-1). Moreover, by simply administering a brief course of IL-1 the authors were able to stimulate arthritis in animals that lacked mast cells. These findings suggest that mast cell IL-1 is needed to marshal leukocytes to affected joints in the initial stages of the inflammatory response yet may be dispensable for the maintenance of arthritis thereafter. Interestingly, in humans, autoantibodies have been observed in serum long before symptoms of rheumatoid arthritis become apparent. If the contribution of mast cells to human rheumatoid arthritis is similar to that described in this mouse model, the compelling question is which factors beyond the presence of autoantibodies dictate the timing of mast cell activation in human disease. Multiple sclerosis is an autoimmune disorder in which neuronal axons of the central nervous system are targeted for demyelination. Lin et al. (2007) recently characterized the role of interferon-g (IFN-g) in the early stages of experimental autoimmune encephalomyelitis (EAE) in mice, which shares some similarities with human multiple sclerosis. EAE can be triggered when mice are immunized with a peptide derived from the myelin/oligoden-drocyte glycoprotein (MOG). Although IFN-g, a proinflammatory cytokine, is generally thought to promote myelin damage in multiple sclerosis and in EAE, there is also evidence that it may have beneficial effects as well. The work by Lin et al. establishes that the timing of IFN-g expression is critical. …


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