Figure 2.

Hypothesis of the contribution of extracellular alarmins to the pathogenesis of Sjögren’s syndrome. Apoptotic and necrotic SGEC are a potent source of extracellular alarmins. Once in the extracellular milieu, they bind to their receptor, leading to the secretion of pro-inflammatory cytokines through the activation of intracellular pathways such as NF-κB or via the activation of NLRP3 inflammasome. DC are activated and are a potent source of IFN-γ. IFN-γ in turn acts on SGEC to further release alarmins in the extracellular milieu, thereby constituting a vicious auto-inflammatory loop. HSP can also be captured by surrounding APC, allowing cross-presentation of the pept i confirm ides by MHC I that further contribute to progression toward autoimmunity by activating CD8+ and CD4+ T cells.