A critical role for the innate immune signaling molecule IRAK-4 in T cell activation.

Suzuki, Nobutaka; Suzuki, Shinobu; Millar, Douglas G; Unno, Midori; Hara, Hiromitsu; Calzascia, Thomas; Yamasaki, Sho; Yokosuka, Tadashi; Chen, Nien-Jung; Elford, Alisha R; Suzuki, Jun-Ichiro; Takeuchi, Arata; Mirtsos, Christine; Bouchard, Denis; Ohashi, Pamela S; Yeh, Wen-Chen; Saito, Takashi

IRAK-4 is a protein kinase that is pivotal in mediating signals for innate immune responses. Here, we report that IRAK-4 signaling is also essential for eliciting adaptive immune responses. Thus, in the absence of IRAK-4, in vivo T cell responses were significantly impaired. Upon T cell receptor stimulation, IRAK-4 is recruited to T cell lipid rafts, where it induces downstream signals, including protein kinase C activation through the association with Zap70. This signaling pathway was found to be required for optimal activation of nuclear factor kappaB. Our findings suggest that T cells use this critical regulator of innate immunity for the development of acquired immunity, suggesting that IRAK-4 may be involved in direct signal cross talk between the two systems.