Cross-regulation of TNF and IFN-α in autoimmune diseases

Proc. Natl. Acad. Sci. USA 102, 3372-7 (2005)

Speaker: 陳煜恬                             Date: 2005/10/19 15:10~16:00

Commentator: 王崇任 醫師                    Place: Room 601

Abstracts:

Cytokines play critical roles in the pathogenesis of autoimmune diseases. In systemic lupus erythematosus (SLE), high level of type I interferons (IFN-αβ) were found to correlate with the disease activity. In the rheumatoid arthritis (RA), TNF was also identified as a major factor in the disease development. For the clinical therapy of RA, anti-TNF antibodies have been though most efficient so far. However, complications such as increased anti-dsDNA antibodies in 15% RA patients undergoing anti-TNF therapy were found.It has not yet been explored whether TNF and IFN-α exist cross-regulatory roles in human autoimmunity. The author reported that TNF regulate IFN-α production through inhibiting the generation of plasmacytoid dendritic cells (pDCs), the potent type I interferons producing cells. Furthermore, TNF also inhibits the releasing process of IFN-α by inducting the maturation of pDCs. These observations might provide explanation for development of lupus-like syndrome in RA patients after anti-TNF therapy.

Reference:

1.          Banchereau, J., et al. Induction of dendritic cell differentiation by IFN-α in systemic lupus Eeythematosus. Science, 294, 1540–1543 (2001).

2.          Smolen, J. S., et al. Safety and efficacy of tumor necrosis factor α blockade in

systemic lupus erythematosus. Arthritis Rheum. 50, 3161–3169 (2004).

3.          Banchereau, J., et al. Cross-regulation of TNF and IFN-α in autoimmune diseases. Proc. Natl. Acad. Sci. USA 102, 3372-7 (2005).