The adaptor Act1 is required for interleukin 17 - Dependent signaling associated with autoimmune and inflammatory disease

Youcun Qian; Caini Liu; Justin Hartupee; Cengiz Zubeyir Altuntas; Muhammet Fatih Gulen; Daniel Jane-Wit; Jianhua Xiao; Yi Lu; Natalia Giltiay; Jinbo Liu; Tomasz Kordula; Qi Wei Zhang; Bruce Vallance; Shadi Swaidani; Mark Aronica; Vincent K. Tuohy; Thomas Hamilton; Xiaoxia Li

doi:10.1038/ni1439

The adaptor Act1 is required for interleukin 17 - Dependent signaling associated with autoimmune and inflammatory disease

Youcun Qian, Caini Liu, Justin Hartupee, Cengiz Zubeyir Altuntas, Muhammet Fatih Gulen, Daniel Jane-Wit, Jianhua Xiao, Yi Lu, Natalia Giltiay, Jinbo Liu, Tomasz Kordula, Qi Wei Zhang, Bruce Vallance, Shadi Swaidani, Mark Aronica, Vincent K. Tuohy, Thomas Hamilton, Xiaoxia Li

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501 Scopus citations

Abstract

T helper cells that produce interleukin 17 (IL-17) are associated with inflammation and the control of certain bacteria. We report here the essential involvement of the adaptor protein Act1 in IL-17 receptor (IL-17R) signaling and IL-17-dependent immune responses. After stimulation with IL-17, recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR' domain, followed by recruitment of the kinase TAK1 and E3 ubiquitin ligase TRAF6, which mediate 'downstream' activation of transcription factor NF-κB. IL-17-induced expression of inflammation-related genes was abolished in Act1-deficient primary astroglial and gut epithelial cells. This reduction was associated with much less inflammatory disease in vivo in both autoimmune encephalomyelitis and dextran sodium sulfate-induced colitis. Our data show that Act1 is essential in IL-17-dependent signaling in autoimmune and inflammatory disease.

Original language	English
Pages (from-to)	247-256
Number of pages	10
Journal	Nature immunology
Volume	8
Issue number	3
DOIs	https://doi.org/10.1038/ni1439
State	Published - Mar 2007

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Qian, Y., Liu, C., Hartupee, J., Altuntas, C. Z., Gulen, M. F., Jane-Wit, D., Xiao, J., Lu, Y., Giltiay, N., Liu, J., Kordula, T., Zhang, Q. W., Vallance, B., Swaidani, S., Aronica, M., Tuohy, V. K., Hamilton, T., & Li, X. (2007). The adaptor Act1 is required for interleukin 17 - Dependent signaling associated with autoimmune and inflammatory disease. Nature immunology, 8(3), 247-256. https://doi.org/10.1038/ni1439

@article{74a6958575bb46278babef73b072f904,

title = "The adaptor Act1 is required for interleukin 17 - Dependent signaling associated with autoimmune and inflammatory disease",

abstract = "T helper cells that produce interleukin 17 (IL-17) are associated with inflammation and the control of certain bacteria. We report here the essential involvement of the adaptor protein Act1 in IL-17 receptor (IL-17R) signaling and IL-17-dependent immune responses. After stimulation with IL-17, recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR' domain, followed by recruitment of the kinase TAK1 and E3 ubiquitin ligase TRAF6, which mediate 'downstream' activation of transcription factor NF-κB. IL-17-induced expression of inflammation-related genes was abolished in Act1-deficient primary astroglial and gut epithelial cells. This reduction was associated with much less inflammatory disease in vivo in both autoimmune encephalomyelitis and dextran sodium sulfate-induced colitis. Our data show that Act1 is essential in IL-17-dependent signaling in autoimmune and inflammatory disease.",

author = "Youcun Qian and Caini Liu and Justin Hartupee and Altuntas, {Cengiz Zubeyir} and Gulen, {Muhammet Fatih} and Daniel Jane-Wit and Jianhua Xiao and Yi Lu and Natalia Giltiay and Jinbo Liu and Tomasz Kordula and Zhang, {Qi Wei} and Bruce Vallance and Shadi Swaidani and Mark Aronica and Tuohy, {Vincent K.} and Thomas Hamilton and Xiaoxia Li",

year = "2007",

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doi = "10.1038/ni1439",

language = "English",

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pages = "247--256",

journal = "Nature immunology",

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Qian, Y, Liu, C, Hartupee, J, Altuntas, CZ, Gulen, MF, Jane-Wit, D, Xiao, J, Lu, Y, Giltiay, N, Liu, J, Kordula, T, Zhang, QW, Vallance, B, Swaidani, S, Aronica, M, Tuohy, VK, Hamilton, T & Li, X 2007, 'The adaptor Act1 is required for interleukin 17 - Dependent signaling associated with autoimmune and inflammatory disease', Nature immunology, vol. 8, no. 3, pp. 247-256. https://doi.org/10.1038/ni1439

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AU - Qian, Youcun

AU - Liu, Caini

AU - Hartupee, Justin

AU - Altuntas, Cengiz Zubeyir

AU - Gulen, Muhammet Fatih

AU - Jane-Wit, Daniel

AU - Xiao, Jianhua

AU - Lu, Yi

AU - Giltiay, Natalia

AU - Liu, Jinbo

AU - Kordula, Tomasz

AU - Zhang, Qi Wei

AU - Vallance, Bruce

AU - Swaidani, Shadi

AU - Aronica, Mark

AU - Tuohy, Vincent K.

AU - Hamilton, Thomas

AU - Li, Xiaoxia

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N2 - T helper cells that produce interleukin 17 (IL-17) are associated with inflammation and the control of certain bacteria. We report here the essential involvement of the adaptor protein Act1 in IL-17 receptor (IL-17R) signaling and IL-17-dependent immune responses. After stimulation with IL-17, recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR' domain, followed by recruitment of the kinase TAK1 and E3 ubiquitin ligase TRAF6, which mediate 'downstream' activation of transcription factor NF-κB. IL-17-induced expression of inflammation-related genes was abolished in Act1-deficient primary astroglial and gut epithelial cells. This reduction was associated with much less inflammatory disease in vivo in both autoimmune encephalomyelitis and dextran sodium sulfate-induced colitis. Our data show that Act1 is essential in IL-17-dependent signaling in autoimmune and inflammatory disease.

AB - T helper cells that produce interleukin 17 (IL-17) are associated with inflammation and the control of certain bacteria. We report here the essential involvement of the adaptor protein Act1 in IL-17 receptor (IL-17R) signaling and IL-17-dependent immune responses. After stimulation with IL-17, recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR' domain, followed by recruitment of the kinase TAK1 and E3 ubiquitin ligase TRAF6, which mediate 'downstream' activation of transcription factor NF-κB. IL-17-induced expression of inflammation-related genes was abolished in Act1-deficient primary astroglial and gut epithelial cells. This reduction was associated with much less inflammatory disease in vivo in both autoimmune encephalomyelitis and dextran sodium sulfate-induced colitis. Our data show that Act1 is essential in IL-17-dependent signaling in autoimmune and inflammatory disease.

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JO - Nature immunology

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The adaptor Act1 is required for interleukin 17 - Dependent signaling associated with autoimmune and inflammatory disease

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