Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjögren's syndrome.
Gene expression analysis of target organs might help provide new insights into the pathogenesis of autoimmune diseases. We used global gene expression profiling of minor salivary glands to identify patterns of gene expression in patients with primary Sjögren's syndrome (pSS), a common and prototypic systemic autoimmune disease. Gene expression analysis allowed for differentiating most patients with pSS from controls. The expression of 23 genes in the IFN pathways, including two Toll-like receptors (TLR8 and TLR9), was significantly different between patients and controls. Furthermore, the increased expression of IFN-inducible genes, BAFF and IFN-induced transmembrane protein 1, was also demonstrated in ocular epithelial cells by quantitative RT-PCR. In vitro activation showed that these genes were effectively modulated by IFNs in salivary gland epithelial cells, the target cells of autoimmunity in pSS. The activation of IFN pathways led us to investigate whether plasmacytoid dendritic cells were recruited in salivary glands. These IFN-producing cells were detected by immunohistochemistry in all patients with pSS, whereas none was observed in controls. In conclusion, our results support the pathogenic interaction between the innate and adaptive immune system in pSS. The persistence of the IFN signature might be related to a vicious circle, in which the environment interacts with genetic factors to drive the stimulation of salivary TLRs.
Gottenberg
Jacques-Eric
JE
Institut Pour la Santé et de la Recherche Médicale E 802 and Service de Rhumatologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, 94275 Le Kremlin Bicêtre, France.
Cagnard
Nicolas
N
Lucchesi
Carlo
C
Letourneur
Franck
F
Mistou
Sylvie
S
Lazure
Thierry
T
Jacques
Sebastien
S
Ba
Nathalie
N
Ittah
Marc
M
Lepajolec
Christine
C
Labetoulle
Marc
M
Ardizzone
Marc
M
Sibilia
Jean
J
Fournier
Catherine
C
Chiocchia
Gilles
G
Mariette
Xavier
X
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007372:Interferons / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology*; D012470:Salivary Glands, Minor / Q000166:cytology / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology
D007372:Interferons