Hiroshi Tanaka and Tadaatsu Imaizumi
Background: Since viral infections activate type I interferon (IFN) pathways and cause subsequent release of IFN-dependent proinflammatory chemokines/cytokines, the innate immune system plays an important role in the pathogenesis of lupus nephritis (LN) as well as systemic lupus erythematosus. With respect to this issue, mesangial chemokine/cytokine expressions via innate immunity reportedly play a pivotal role in the pathogenesis of LN. Also, it has been reported that pediatric-onset active LN is found as having more severe acute inflammation than that of adult cases. Therefore, viral or “pseudoviral” infections may be attributable, at least in part, to the pathogenesis of LN, especially in pediatric-onset cases.
Methods: So far, we have examined the toll-like receptor (TLR) 3 signaling cascades treated with polyinosinicpolycytidylic acid (poly IC), a synthetic analogue of viral dsRNA, that makes “pseudoviral” infection in cultured human mesangial cells (MCs).
Results: We found that the activation of mesangial TLR3 upregulated the expression of functional molecules acting as monocyte/macrophage and lymphocyte chemoattractants in MCs. Further, intense glomerular expressions of these functional molecules were observed in biopsy specimens from children with active LN.
Conclusion: These observations further support the implication of viral and “pseudoviral” immunity in the pathogenesis of active LN, especially in pediatric-onset cases.
