**6. References**


progression of lupus-associated renal injury, and IFN-γ is one of the major Th1 type cytokines with potent proinflammatory effects that exerts its effects through the upregulation of IFNinducible genes (Patole et al., 2006), we examined the effects of IFN-γ on the expression of RIG-I in human mesangial cells. As a result, IFN-γ treatment resulted in a concentration-dependent upregulation of the expression of RIG-I mRNA and protein in human mesangial cells. Treatment of cells with IFN-γ also induced the expression of mRNA of both IRF 1 and IRF7, which are important IFN-inducible transcriptional factors. Furthermore, knockdown of RIG-I expression by RNA interference inhibited the IFN-γ-induced expression of IRF7, but not that of IRF1. In contrast, IFN-γ did not induce the expression of IFN-β, which is known to be a

Interestingly, pretreatment of cells with dexamethasone inhibited the IFN-γ-induced expression of monocyte chemoattractant protein (MCP)-1 mRNA but did not affect the induction of RIG-I or IRF7 mRNA in mesangial cells. The induction of MCP-1 mRNA by IFN-γ was not inhibited by the knockdown of NF-κB p65, indicating that the NF-κB signaling pathway was not involved. Our results suggest selective regulation of the expression of IRFs by RIG-I in human mesangial cells. The function of IRF7 has been well studied, mainly in dendritic cells and in mouse embryonic fibroblasts, and IRF7 is thought to be an important transcriptional factor that affects anti-viral responses by inducing the

**3.2 Treatment of pediatric-onset lupus nephritis by direct targeting the IFN-γ/RIG-**

Although the functional significance of IRF7 expression in mesangial cells remains to be elucidated, our recent observations suggest that the IFN-γ/RIG-I/IRF7 signaling pathways may be involved in the pathogenesis of lupus nephritis. We believe that the involvement of the newly observed IFN-γ/RIG-I/IRF7 pathway in mesangial cells may contribute to mesangial inflammation, and the intervention of this signaling pathway may lead to the development of optimal future therapeutic strategies for patients with lupus nephritis. However, further clinical and experimental issues remain to be examined in future studies.

Part of these studies was supported by a Grant from the Japan Society for the Promotion of Science (#21591259 and #22591175) and a grant from The Mother and Child Health

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production of type I IFN (Honda et al., 2005).

**I/IRF7 pathway** 

**4. Acknowledgements** 

Foundation, Osaka, Japan.

None declared.

**6. References** 

**5. Conflict of interest statement** 

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**15** 

*Australia* 

**Recent Advances in the Treatment of** 

**Neurological Autoimmune Disorders** 

*Deakin University Waurn Ponds, Geelong,* 

Jagat R. Kanwar\*, Bhasker Sriramoju and Rupinder K. Kanwar *Laboratory of Immunology and Molecular Biomedical Research (LIMBR), Centre for Biotechnology and Interdisciplinary Biosciences (BioDeakin), Institute for Technology in Nanomedicine & Research Innovation,* 

Autoimmune diseases are a complex group of diseases arising because of the breakdown of narrow margin that exists between the immunity and tolerance. In simpler terms either T or B-cells or both are activated in the absence of a progressive infection or any other noticeable cause (Davidson & Diamond, 2001). Unable to distinguish self from non self, the renegade immune cells pose a serious threat to self molecules leading to severe destruction. The precise mechanisms that drive this event are still unclear but, most of the studies identified that genetics, environment and infections will have a role in triggering the autoimmune attack (Smith et al., 1999). An approximate of 5% of the population in western countries are currently the victims of these diseases and in this component, a major proportion of them are females displaying a higher risk of incidence (Jacobson, 1997; Kanwar, 2005). Added to this, the general ailments of the humans like atherosclerosis and gastrointestinal disturbances are found to be associated with an autoimmune component, predisposing the risk of developing an autoimmune disease (Ross, 1990, Galperin & Gershwin 1997).The influence of hormones cannot be neglected as preclinical studies have witnessed the role of oestrogen in the emergence of autoimmune diseases while testosterone was found to lower the risk in lupus prone mice (Sakic, 1998; Roubinian et al., 1978). Few epidemiological studies also revealed the preponderance of autoimmune diseases mediated by the nocturnal hormone, melatonin (Cutolo, 2003). In addition, cortisol levels and the secondary events like stress were also found to influence the autoimmune disease generation (Webster et al, 1998). Since ages, the basic principle of immunology has been the concept of clonal deletion of autoreactive immune cells and generation of a mature T & B-cell repertoire that could distinguish self from non self. The formation and survival of mature immune repertoire, always demands prolonged auto antigen exposure acknowledging the physiological importance of autoreactivity (Goldrath & Bevan, 1999; Gu et al., 1991). Though structural resemblances exist between self and non self antigens the attack is directed against self antigens under stimulatory conditions like the presence of infections, cytokines etc (Silverstein & Rose, 2000; Kanwar, 2005; Kanwar et al, 2009). Thus it is always fascinating to find answers for how the physiology of autoimmunity is turned to pathology and how the immune cells enforce their attack. This review focuses on introduction to immunity, pathology of autoimmune diseases and their treatments along with recent advancements.

**1. Introduction** 

