The role of innate immunity in autoimmune tissue injury.

PURPOSE OF REVIEW

To discriminate the pathomechanims of autoimmunity from that of autoimmune tissue injury, for example, in systemic lupus erythematosus, with a special focus on the role of innate pathogen recognition receptors in lupus nephritis.

RECENT FINDINGS

Toll-like receptors mediate immune activation upon the recognition of pathogens in different extracellular and intracellular compartments. Systemic lupus erythematosus appears to be one of the conditions in which self-nucleic acid formats can activate innate viral nucleic acid recognition receptors like TLR-7 or TLR-9. This process can modulate the tolerance mechanisms by activating antigen-presenting cells in lymphoid organs. This mechanism does also occur at the tissue level in tissue macrophages, dendritic cells, B cells and nonimmune cells. For example, nonimmune renal cells express a limited set of functional Toll-like receptors that trigger local cytokine and chemokine release in lupus nephritis upon Toll-like receptor activation.

SUMMARY

In systemic lupus erythematosus, autoantibodies and expansion of autoreactive T cells indicate systemic autoimmunity, but organ damage involves additional mechanisms of inflammation and tissue remodelling. Targeting local release of proinflammatory cytokines, for example, by blocking Toll-like receptors or single cytokines, may enhance treatment efficacy in autoimmunity without increasing systemic immunosuppression.