RNA sensing by conventional dendritic cells is central to the development of lupus nephritis
Celhar T., Hopkins R., Thornhill SI., De Magalhaes R., Hwang S-H., Lee H-Y., Yasuga H., Jones LA., Casco J., Lee B., Thamboo TP., Zhou XJ., Poidinger M., Connolly JE., Wakeland EK., Fairhurst A-M.
Significance Systemic lupus erythematosus is a complex autoimmune disease where genetic and environmental factors play equally important roles. Recent research has identified that upregulation of the innate immune Toll-like receptor 7 (TLR7) is fundamental for the development of severe disease. In our Sle1 Tg7 model system, we show that increased expression of TLR7 in dendritic cells (DCs) is important for the development of kidney disease. Furthermore, we identify conventional CD11b + DCs infiltrating the glomeruli of diseased mice. In a resting state, human myeloid DCs express negligible levels of TLR7. However, exposure to multiple stimuli results in a dramatic increase in expression. Together, these findings suggest a role for myeloid DC-TLR7 in clinical disease and that TLR7 expression in this cellular compartment may represent a novel target for therapeutic investigation.