Figure 3: Probable factors and causes (?), which may affect function and structure in lacrimal and salivary glands in nonimmune injury (Hypothesis). Environmental factors (especially viruses and bacteria) may play a role in both nonimmune and immune mechanisms. Self-reporting symptoms in patients with SjS may be the results of cumulative effects of nonimmune and immune mechanisms. Apart from functional changes, the syndrome may be also characterized by structural abnormalities of microenvironmental components (niche) which include endothelial cells (Ec) in capillary, myoepithelium (Me), nervous fibers (An), basement membranes (Bm), tight junction (Tj), duct (De), and secretory acinar epithelial cells. In addition, dendritic cells (Dc), which appear in pSjS patients but not in healthy controls [55], may play an important role in immune attack together with effectors (E). Effect of circulating cytokine* and gene* in nonimmune phase and role of locally produced cytokine** and abnormal gene** being responsible for destruction of self-torerance in immune phase are indicated. In this figure, detailed immune mechanisms including the role of environmental factors are omitted. E: effector cells (e.g., cytotoxic T cell, Th1 cell, B cell, and plasma cell).