Salivary epithelial cells from Sjogren’s syndrome patients are highly sensitive to anoikis induced by TLR-3 ligation

Role of toll-like receptors in primary Sjögren’s syndrome with a special emphasis on B-cell maturation within exocrine tissues

“…Moreover, TLR3 stimulation can trigger epithelial cells into apoptosis. Those from SGs of SS patients appear highly sensitive to this phenomenon confirming the role of TLRs in the pathophsyiology of SS [33]. This hypothesis is reinforced by the observation made in the female NZB/NZW F1 mice.…”

The role of intrinsic epithelial activation in the pathogenesis of Sjögren’s syndrome

“…In fact, TLR expressed by SGEC were shown to possess similar function, as this was illustrated by the upregulation of surface expression of MHC-I, CD54/ICAM-1, CD40, and CD95/Fas proteins following SGEC stimulation with the appropriate TLR ligands [43]. Apart from the induction of surface activation molecules, TLR-3 triggering in cultured SGEC using polyI:C was also found to induce severe detachment of SGEC from substratum and subsequent induction of apoptosis, a phenomenon suggestive of anoikis (detachmentinduced apoptosis) [45]. PolyI:C-induced anoikis in SGEC could not be inhibited by blocking antibodies to CD95/Fas, IFN-b, IFN-g or TNFa, but was associated with the upregulation of the pro-apoptotic Bmf, BimEL and Bax and the downregulation of the pro-survival Bcl-2, as indicated by real-time PCR analyses [45].…”

TLR9 responses of B cells are repressed by intravenous immunoglobulin through the recruitment of phosphatase

“…Aberrant TLR3 ligation participates to the activation of programmed-cell death in salivary epithelial cells from Sjögren's syndrome patients [13]. Furthermore, TLR9 stimulation may exacerbate B cell hyperactivity, and thereby favors the synthesis of antidsDNA Ab in SLE [14].…”