Selective recruitment of CCR6-expressing cells by increased production of MIP-3 alpha in rheumatoid arthritis

Infiltration of various types of leucocytes has been shown to play a crucia l role in the pathogenesis of rheumatoid arthritis (RA). Macrophage inflamm atory protein-3 alpha (MIP-3 alpha) is a recently identified chemokine whic h is a selective chemoattractant for leucocytes such as memory T cells, nai ve B cells and immature dendritic cells. In this study, we investigated the expression of MIP-3 alpha and its specific receptor CCR6 in the inflamed j oints of patients with RA. Increased amounts of MIP-3 alpha were found by E LISA in synovial fluids (SF) of patients with RA. MIP-3 alpha was apparentl y detected in all synovial tissue specimens of RA patients (n = 6), but it could not be detected in that of osteoarthritis (OA) patients (n = 4). Expr ession of MIP-3 alpha was detected especially in the sublining layer, and i nfiltrating mononuclear cells in RA synovial tissue. Gene expression of MIP -3 alpha was also found in six out of 11 RA-synovial fluid cells by RT-PCR. Cultured synovial fibroblasts derived from either RA or OA patients were c apable of producing MIP-3 alpha in response to IL-1 beta and TNF alpha in v itro. Furthermore, expression of CCR6 was found in infiltrating mononuclear cells in the cellular clusters and around the vessels of RA synovial tissu e. These findings indicate that increased production of MIP-3 alpha may con tribute to the selective recruitment of CCR6-expressing cells in RA.