Interferon Regulatory Factor 4 (IRF4)

By fluorescence and confocal microscopy, Negishi et al. (2005) demonstrated that IRF4 interacted with MYD88  in the cytoplasm of human embryonic kidney cells. Mutation and coimmunoprecipitation analysis showed that IRF4 interacted with the TIR/IL1 region of MYD88.

IRF4 inhibited interaction of MYD88 with IRF5, which interacts with the same central region of MYD88 as IRF4, but it did not block interaction of MYD88 with IRF7 , which binds to the N terminus. IRF5-dependent gene induction was inhibited by IRF4, and IRF4-deficient macrophages were hyperresponsive to Toll-like receptor (TLR) stimuli. Negishi et al. (2005) concluded that IRF4 negatively regulates TLR signaling by selectively competing with IRF5.