Autoantigen signalling through chemokine receptors.
OBJECTIVE
Recent studies have shown that disease-associated self-antigens activate chemokine receptors. This review focuses on the mechanics of autoantigen interaction with select chemokine receptors, how these migratory signals are amplified and discusses the possibility that chemokine receptors can be valuable therapeutic targets in the prevention and treatment of autoimmune disease.


RESULTS
We have recently shown that most autoantigens are chemotactic for immature dendritic cells, suggesting that autoantigens have the potential to bridge the innate and adaptive immune systems. Autoantigens also induce other leukocytes expressing their responsive chemokine receptor to migrate. These newly recruited leukocytes, in response to proinflammatory mediators, simulate the surrounding tissues to release chemokines. Several groups have reported increases in both select chemokines and chemokine receptors in inflamed tissues. Taken together, these studies suggest that autoantigens initiate leukocyte migration into damaged and inflamed tissue that leads to the subsequent amplification of the inflammatory response.


CONCLUSIONS
Most autoantigens induce chemokine receptor mediated cell migration, therefore targeting chemokine receptors for either prevention or therapy has great potential to limit autoimmune diseases.
Howard
Om Zack
OZ
Center for Cancer Research, Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, Maryland, USA. howardz@mail.ncifcrf.gov
D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
D001324:Autoantigens; D019707:Receptors, Chemokine