A critical role for the innate immune signaling molecule IRAK-4 in T cell activation.
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.
Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan.
Nobutaka
N
Suzuki
Shinobu
S
Suzuki
Douglas G
DG
Millar
Midori
M
Unno
Hiromitsu
H
Hara
Thomas
T
Calzascia
Sho
S
Yamasaki
Tadashi
T
Yokosuka
Nien-Jung
NJ
Chen
Alisha R
AR
Elford
Jun-Ichiro
J
Suzuki
Arata
A
Takeuchi
Christine
C
Mirtsos
Denis
D
Bouchard
Pamela S
PS
Ohashi
Wen-Chen
WC
Yeh
Takashi
T
Saito
D000818:Animals; D004789:Enzyme Activation; D007113:Immunity, Innate; D053592:Interleukin-1 Receptor-Associated Kinases; D007527:Isoenzymes / Q000378:metabolism; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D000074121:Protein Kinase C-theta; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
D007527:Isoenzymes; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D017853:Phosphotransferases (Alcohol Group Acceptor); D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D053592:Interleukin-1 Receptor-Associated Kinases; C507774:Irak4 protein, mouse; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta