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B-cell-activating factor (BAFF) plays a key role in promoting activation of autoimmune B cells. This cytokine may be expressed in and secreted by salivary gland epithelial cells (SGEC) after stimulation with type I IFN or viral or synthetic dsRNA. Because this BAFF expression depends only in part on endosomal TLR and type I IFN, we investigated whether other dsRNA sensors could be implicated in BAFF expression. Using human SGEC, we confirmed the partial dependence of BAFF expression on TLR-3 by replicating the partial inhibition of BAFF expression observed upon endosomal inhibition using TLR-3 or Toll/IL-1R domain-containing protein inducing IFN-beta silencing mRNA, but not with TLR-7 silencing mRNA. Melanoma differentiation-associated gene 5 silencing mRNA had no effect on BAFF expression, but retinoic acid-inducible gene I silencing mRNA had a slight effect observed following infection with dsRNA reovirus-1. Inhibition of RNA-activated protein kinase (PKR) by 2-aminopurine completely abolished both BAFF mRNA and protein production after reovirus-1 infection and poly(I:C) stimulation through NF-kappaB and p38 MAPK pathways, with the latter implicated only after poly(I:C) stimulation. Thus, PKR is the dsRNA sensor implicated in BAFF induction in SGEC after dsRNA stimulation. In autoimmune diseases, PKR may be an interesting target for preventing BAFF following the induction of innate immunity.

B cell activating factor (BAFF) plays a key role in promoting B lymphocyte activation. We investigated whether danger signals induce BAFF secretion by cultured salivary gland epithelial cells (SGEC), which are the target of primary Sjögren's syndrome, a prototypic systemic autoimmune disease. SGEC cultures were established from minor salivary glands obtained from ten patients with pSS or sicca symptoms. BAFF mRNA and protein were measured after stimulation of the different Toll-like receptors (TLR) by agonists or viruses. The expression of TLR2, -3, and -7 was detected in SGEC. Poly (I:C) (a synthetic TLR3 agonist) and reovirus-1 (a dsRNA virus) induced high expression of BAFF mRNA (multiplied by a factor of 246 +/- 39 (SEM) and 347 +/- 66, respectively) and of BAFF protein secretion (58.49 +/- 4.34 pg/mL and 69.73 +/- 5.67). Inhibition of both the endosomal (by chloroquine) and IFN (by anti-IFNAR antibody) pathways partly inhibited BAFF expression. Treatment with both dsRNA virus and poly (I:C) induced high levels of BAFF mRNA and protein expression by SGEC, through pathways dependent on and independent of TLR and dependent on and independent of IFN. BAFF induction by target organs of autoimmune diseases after viral infection may be a link between innate immunity and autoimmunity.