The role of innate immunity in autoimmune tissue injury.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Allam
Ramanjaneyulu
R
Medical Policlinic, University of Munich, Munich, Germany.
Anders
Hans-Joachim
HJ
D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
D001323:Autoantibodies; D051193:Toll-Like Receptors