Viruses induce high expression of BAFF by salivary gland epithelial cells through TLR- and type-I IFN-dependent and -independent pathways.
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.
Ittah
Marc
M
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.
Miceli-Richard
Corinne
C
Gottenberg
Jacques-Eric
JE
Sellam
Jérémie
J
Eid
Pierre
P
Lebon
Pierre
P
Pallier
Coralie
C
Lepajolec
Christine
C
Mariette
Xavier
X
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
D053264:B-Cell Activating Factor; D007370:Interferon Type I; D008024:Ligands; C505719:TNFSF13B protein, human; D051193:Toll-Like Receptors