Figure 1.

The interplay between environmental factors and genetic susceptibilities in shaping immune dysregulation. Genetic susceptibilities could lead to immune dysregulation via different mechanisms including (1) defective apoptotic cell clearance, (2) defective apoptosis, and (3) loss of suppressive regulatory controls. Collectively they lead to disrupted cytokine signals and hyperactivation of autoreactive T and B cells, invigorating a series of tissue damage in various manifestations. In SLE, the manifestations could be presented as splenomegaly, lymphadenopathy, nephritis and arthritis. Environmental triggers either augment or mitigate these mechanisms to shape the autoimmunity.