**3. Physiopathology of Sjögren's Syndrome**

SS is considered as a multifactorial process originating from the interaction between genetic factors and exogenous and endogenous agents able to trigger an abnormal autoimmune response mediated in particular by T and B lymphocytes [9]. The inflammation sustains, perpetuates and amplifies tissue damage and leads to a progressive functional impairment of the affected organs and a chronic inflammatory environment. Three recurrent events are generally associated with SS: (1) a trigger phase induced by environmental factors under specific epigenetic factors, genetic predisposition and hormonal regulation; (2) the dysregulation of normal salivary gland epithelial cell (SGEC) function; (3) a chronic inflammation characterized by SG infiltration made of lymphocytic cells, lymphocytes B hyperactivity and autoantibodies production [10] (Figure 1).

**Figure 1.** Overview of physiopathological mechanism underlying Sjögren's syndrome (SS). Environmental triggers, such as viral infections, genetic predispositions, epigenetics and sex hormone deregulation, cause the disruption of salivary gland epithelial cell (SGEC), the production of type I interferon (IFN) and other cytokines such as B cell Activating Factor of the tumour necrosis factor (TNF) Family (BAFF) [11] and the alteration of proteins involved in saliva secretion. Dendritic cells, as well as SGEC acquire the characteristics of antigen-presenting cells capable of processing viral and self-antigens, leading to the activation of autoreactive T and B cells. Autoreactive T cells induce tissue damage through the release of cytotoxic granules and cause the exposure of autoantigens on the surface of SGEC. In addition, activated B cells produce autoantibodies that induce SGEC apoptosis and create an inflammatory microenvironment. This complex mechanism triggers a self-perpetuating cycle of autoimmunity.
