Cytokines swing between good and bad in the war on autoimmune arthritis
Rheumatoid arthritis (RA) is an autoimmune disease that targets the bone and cartilage. The cytokines BLyS and APRIL are present in the serum of RA patients. In a paper appearing online on October 20 in advance of print publication of the November issue of the Journal of Clinical Investigation, Cornelia Weyand and colleagues from Emory University examine whether BLyS and APRIL sustain B cell function in arthritic lesions, providing a T cell-independent mechanism of autoimmunity.
The authors studied BLyS and APRIL production, and evidence for their receptors, in 72 tissue biopsies comprising 3 different types of synovitis typical of RA. While BLyS derived from macrophages, APRIL was produced by DCs. The TACI receptor for these two cytokines was expressed on plasma cells, B cells, and T cells. However, TACI positive T cells were absent in germinal-center containing RA lesions. To block the action of BLyS and APRIL in the disease lesions the authors treated human synovium-SCID mouse chimeras with the decoy receptor TACI:Fc. Treatment destroyed germinal centers, blocked immunoglobulin production and inhibited expression of the T cell cytokine IFN-_. Surprisingly, inhibition of BLyS and APRIL in other types of synovitis enhanced IFN-_ production.
Thus, BLyS and APRIL regulate both B and T cell function and have both pro- and anti-inflammatory actions in RA. These data help explain why RA encompasses several types of synovial inflammation, with distinct disease mechanisms and differential responsiveness to therapy.
TITLE: BLyS and APRIL in Rheumatoid Arthritis
View the PDF of this article at: the-jci.org/article.php?id=25265
Stacie Bloom
The authors studied BLyS and APRIL production, and evidence for their receptors, in 72 tissue biopsies comprising 3 different types of synovitis typical of RA. While BLyS derived from macrophages, APRIL was produced by DCs. The TACI receptor for these two cytokines was expressed on plasma cells, B cells, and T cells. However, TACI positive T cells were absent in germinal-center containing RA lesions. To block the action of BLyS and APRIL in the disease lesions the authors treated human synovium-SCID mouse chimeras with the decoy receptor TACI:Fc. Treatment destroyed germinal centers, blocked immunoglobulin production and inhibited expression of the T cell cytokine IFN-_. Surprisingly, inhibition of BLyS and APRIL in other types of synovitis enhanced IFN-_ production.
Thus, BLyS and APRIL regulate both B and T cell function and have both pro- and anti-inflammatory actions in RA. These data help explain why RA encompasses several types of synovial inflammation, with distinct disease mechanisms and differential responsiveness to therapy.
TITLE: BLyS and APRIL in Rheumatoid Arthritis
View the PDF of this article at: the-jci.org/article.php?id=25265
Stacie Bloom
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