Innate Immunity as a Hired Gun : But Is It Rheumatoid Arthritis?

Inflammatory forms of arthritis such as rheumatoid arthritis (RA) are chronic diseases that primarily affect peripheral synovial joints. The pathogenesis of RA is multifactorial, including genetic influences on susceptibility, postnatal events in immune maturation, environmental factors, and amplifying cytokine networks that perpetuate inflammation (1). Many elegant models of transgenic and gene disrupted mice provide insight into the pathogenic mechanisms of these diseases. Some of these models such as the K/BxN, TNFα transgenic, IL-1 receptor antagonist deficient, and human T lymphotropic virus type I (HTLV-I) tax transgenic mice develop spontaneous disease. Other models rely on the induction of disease by collagen inoculation in DBA/J or humanized HLA transgenic mice, direct intraarticular antigen or oligonucleotide administration, injection with bacterial cell walls, or by creating immune complexes. The panoply of pathogenic mechanisms illustrates the wide variety of initiating circumstances that can ultimately lead to joint damage....