The protective effect of the antiToll- like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA

Toll- like Receptor 9 ( TLR9) is an innate immune receptor recognizing microbial DNA. TLR9 is also activated by self- derived DNA, such as mitochondrial DNA, in a variety of inflammatory diseases. We show here that TLR9 activation in vivo is controlled by an anti- TLR9 monoclonal Ab ( mAb). A newly established mAb, named NaR9, clearly detects endogenous TLR9 expressed in primary immune cells. The mAb inhibited TLR9- dependent cytokine production in vitro by bone marrow- derived macrophages and conventional dendritic cells. Furthermore, NaR9 treatment rescued mice from fulminant hepatitis caused by administering the TLR9 ligand CpGB and D-(+)- galactosamine. The production of proinflammatory cytokines induced by CpGB and D-(+)- galactosamine was significantly impaired by the mAb. These results suggest that a mAb is a promising tool for therapeutic intervention in TLR9dependent inflammatory diseases.