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.
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.
Authors: Juan M Mejia-Vilet; Samir V Parikh; Huijuan Song; Paolo Fadda; John P Shapiro; Isabelle Ayoub; Lianbo Yu; Jianying Zhang; Norma Uribe-Uribe; Brad H Rovin Journal: Nephrol Dial Transplant Date: 2019-07-01 Impact factor: 5.992
Authors: Yi Ting Koh; John C Scatizzi; Jennifer D Gahan; Brian R Lawson; Roberto Baccala; K Michael Pollard; Bruce A Beutler; Argyrios N Theofilopoulos; Dwight H Kono Journal: J Immunol Date: 2013-04-15 Impact factor: 5.422