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Basic Science for the Clinician 27: Toll-Like Receptors and Nucleotide Oligomerization Domains

Sigal, Leonard H. MD, FACP, FACR

JCR: Journal of Clinical Rheumatology: June 2005 - Volume 11 - Issue 3 - p 176-179
doi: 10.1097/01.rhu.0000165290.47682.57
Basic Science

Ancient protective mechanisms are in place, deep within our defenses against infection and malignancy, often unappreciated until homologous proteins found within less phylogenetically advanced organisms are identified. Such is the case with 2 major recent finds, the Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD) families of innate immunity molecules. These families of receptors have high specificity, limited heterogeneity, and no plasticity; nonetheless, they play a pivotal role in rapid initial defenses against pathogens. Moreover, studies of the mechanisms of TLRs and NODs show how they and IL-1 and IL-18 stand at the threshold of the adaptive immune response and help to accelerate specific immune responsivity. Nonspecific reactivity of these preprogrammed receptors may be how relatively nonpathogenic organisms like yersinia and chlamydia may drive the inflammation of reactive arthritis and atherosclerosis. The inflammation of rheumatoid arthritis may be magnified, if not initiated, by these innate mechanisms as well.

These important components of innate immunity are initial defenses against pathogens and may have roles in the pathogenesis of reactive arthritis and even rheumatoid arthritis.

From the Pharmaceutical Research Institute/Bristol-Myers Squibb, Princeton, New Jersey, and the Division of Rheumatology and Connective Tissue Research, the Departments of Medicine, Pediatrics, and Molecular Genetics & Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey.

Reprints: Leonard H. Sigal, MD, Pharmaceutical Research Institute/Bristol-Myers Squibb, J.3100, PO Box 4000, Princeton, NJ 08543-4000. E-mail:

© 2005 Lippincott Williams & Wilkins, Inc.