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

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

doi:10.1126/science.1124256

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

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

Research output: Contribution to journal › Article › peer-review

Abstract

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 Cθ activation through the association with Zap70. This signaling pathway was found to be required for optimal activation of nuclear factor κB. 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.

Original language	English
Pages (from-to)	1927-1932
Number of pages	5
Journal	Science
Volume	311
Issue number	5769
DOIs	https://doi.org/10.1126/science.1124256
Publication status	Published - 31 Mar 2006

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Millar, D., Suzuki, N., Suzuki, S., Millar, D. G., Unno, M., Hara, H., Calzascia, T., Yamasaki, S., Yokosuka, T., Chen, N. J., Elford, A. R., Suzuki, J. I., Takeuchi, A., Mirtsos, C., Bouchard, D., Ohashi, P. S., Yeh, W. C., & Saito, T. (2006). A critical role for the innate immune signaling molecule IRAK-4 in T cell activation. Science, 311(5769), 1927-1932. https://doi.org/10.1126/science.1124256

@article{efc16937d6bb4e30a368e320f32dee71,

title = "A critical role for the innate immune signaling molecule IRAK-4 in T cell activation",

abstract = "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 Cθ activation through the association with Zap70. This signaling pathway was found to be required for optimal activation of nuclear factor κB. 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.",

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

year = "2006",

month = mar,

day = "31",

doi = "10.1126/science.1124256",

language = "English",

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Millar, D, Suzuki, N, Suzuki, S, Millar, DG, Unno, M, Hara, H, Calzascia, T, Yamasaki, S, Yokosuka, T, Chen, NJ, Elford, AR, Suzuki, JI, Takeuchi, A, Mirtsos, C, Bouchard, D, Ohashi, PS, Yeh, WC & Saito, T 2006, 'A critical role for the innate immune signaling molecule IRAK-4 in T cell activation', Science, vol. 311, no. 5769, pp. 1927-1932. https://doi.org/10.1126/science.1124256

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T1 - A critical role for the innate immune signaling molecule IRAK-4 in T cell activation

AU - Millar, Douglas

AU - Suzuki, Nobutaka

AU - Suzuki, Shinobu

AU - Millar, Douglas G.

AU - Unno, Midori

AU - Hara, Hiromitsu

AU - Calzascia, Thomas

AU - Yamasaki, Sho

AU - Yokosuka, Tadashi

AU - Chen, Nien Jung

AU - Elford, Alisha R.

AU - Suzuki, Jun Ichiro

AU - Takeuchi, Arata

AU - Mirtsos, Christine

AU - Bouchard, Denis

AU - Ohashi, Pamela S.

AU - Yeh, Wen Chen

AU - Saito, Takashi

PY - 2006/3/31

Y1 - 2006/3/31

N2 - 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 Cθ activation through the association with Zap70. This signaling pathway was found to be required for optimal activation of nuclear factor κB. 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.

AB - 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 Cθ activation through the association with Zap70. This signaling pathway was found to be required for optimal activation of nuclear factor κB. 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.

U2 - 10.1126/science.1124256

DO - 10.1126/science.1124256

M3 - Article

C2 - 16574867

SN - 0036-8075

VL - 311

SP - 1927

EP - 1932

JO - Science

JF - Science

IS - 5769

ER -

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

Abstract

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