LRRFIP2 Negatively Regulates Trif-dependent TLR Signaling In Macrophages

Toll like receptor is the first line of the defensive mechanisms that protect hosts from invading microbial pathogens. Better understanding how TLR signaling is regulated will obviously facilitate the development of new strategies to control TLR-mediated inflammatory diseases. In the present study, we demonstrate that LRR FLII-interacting protein 2(LRRFIP2/FLAP2) is a negative regulator of Trif-dependent TLR signal. LRRFIP2 expression reduces Trif-activated IFN-βand pro-inflamation cytokines expression. LRRFIP2 inhibits poly(I:C)-induced activation of ERK1/2, JNK1/2 and p38 MAPK as well as LPS-induced activation of IRF3 to inhibit the Trif-dependent signal transduction. Given the pivotal roles of Trif in controlling immune responses, our findings will obviously facilitate the development of new strategies to control Trif-mediated inflammatory diseases.