Systemic increase in type I interferon activity in Sjögren's syndrome: a putative role for plasmacytoid dendritic cells.
In the salivary glands of primary Sjögren's syndrome (pSjS) patients, type I IFN activity is increased, but systemic levels of type I IFN proteins are rarely detected. This study focused on the systemic activity of type I IFN in pSjS, as well as the role of peripheral plasmacytoid dendritic cells (pDC). Monocytes obtained from pSjS patients showed an increased expression of 40 genes. Twenty-three of these genes (58%), including IFI27, IFITM1, IFIT3 and IFI44, were inducible by type I IFN. pSjS serum had an enhanced capability of inducing IFI27, IFITM1, IFIT3 and IFI44 in the monocytic cell line THP-1, likely due to the action of IFN-beta. This effect could be inhibited by blocking the type I IFN receptor, supporting a high type I IFN bioactivity in pSjS serum. In addition, circulatory pDC showed increased expression of CD40. This expression was correlated to the expression level of the type I IFN-regulated genes IFI27 and IFITM1 in monocytes of the same individual. This study indicates that the increased type I IFN activity observed in pSjS patients is not only a local but also a systemic phenomenon and points to pDC as a possible source of this activity.
Wildenberg
Manon E
ME
Department of Immunology, Erasmus MC, Rotterdam, The Netherlands. m.wildenberg@erasmusmc.nl
van Helden-Meeuwsen
Cornelia G
CG
van de Merwe
Joop P
JP
Drexhage
Hemmo A
HA
Versnel
Marjan A
MA
D000328:Adult; D000368:Aged; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007370:Interferon Type I / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
D019013:CD40 Antigens; D007370:Interferon Type I