title: Viruses induce high expression of BAFF by salivary gland epithelial cells through TLR- and type-I IFN-dependent and -independent pathways.
abstract: 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.
authors: Rhumatologie, Institut Pour la Santé et la Recherche Médicale INSERM U 802, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud 11, Le Kremlin Bicêtre, France.
authors: Marc
authors: M
authors: Ittah
authors: Corinne
authors: C
authors: Miceli-Richard
authors: Jacques-Eric
authors: JE
authors: Gottenberg
authors: Jérémie
authors: J
authors: Sellam
authors: Pierre
authors: P
authors: Eid
authors: Pierre
authors: P
authors: Lebon
authors: Coralie
authors: C
authors: Pallier
authors: Christine
authors: C
authors: Lepajolec
authors: Xavier
authors: X
authors: Mariette
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007370:Interferon Type I / Q000378:metabolism*; D008024:Ligands; D030102:Orthoreovirus, Mammalian / Q000276:immunology; D012469:Salivary Glands / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism*; D014709:Vero Cells; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D007370:Interferon Type I; D008024:Ligands; C505719:TNFSF13B protein, human; D051193:Toll-Like Receptors