| Abstract |
SLE is a systemic, inflammatory, autoimmune disease characterized by the presence of anti-nuclear antibodies in the serum of patients and an oscillation of disease symptoms with periods of increased disease activity (flares) followed by quiescent periods (remissions) and can cause severe damage to a variety of organs and systems such as the brain; kidney and blood vessels (Bertsias GK et al. 2010). Interestingly, lupus affects mostly females (9:1 female to male ratio) with blacks, Asians, Hispanics and Native Americans showing higher susceptibility than whites (Ippolito et al. 2011; Pisetsky DS, et al. 2001; Rus V, et al. 2001). The sex bias of SLE is probably the result of the presence of estrogen receptors on the surface of immune cells and a direct effect on the regulation of cellular responses by these hormones (Rubtsov AV, et al. 2010).
Although the exact etiology of SLE is yet unknown, both environmental and genetic factors contribute to its pathogenesis (Miller et al. 2007; Zandman-Goddard G, et al. 2012). The contribution of environmental factors is believed to be due to robust activation of both the innate and adaptive immune system in individuals genetically predisposed towards autoimmunity. On the other hand, several intrinsic immune abnormalities have been associated with SLE development and severity. Key factors in the establishment of a predisposition towards lupus include aberrancies in clearance of apoptotic and netotic material. Impaired clearance of such material can provide the immune system with a plethora of self-antigens that would otherwise be absent (Bouts YM, et al. 2012). The effect of impaired clearance of cellular debris is further enhanced by the induction of post-translational modifications and cleavage of proteins present in present in apoptotic blebs. Such modifications are believed to generate neo-antigens that are recognized as danger signals and activate the immune system (Cline AM, et al. 2004; Biermann M, et al. 2013).
A.2
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Regulation of immune responses via co-signaling receptors in human and animal immunity models
