The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation

Muhammet F. Gulen, Zizhen Kang, Katarzyna Bulek, Wan Youzhong, Tae Whan Kim, Yi Chen, Cengiz Z. Altuntas, Kristian Sass Bak-Jensen, Mandy J. McGeachy, Jeong Su Do, Hui Xiao, Greg M. Delgoffe, Booki Min, Jonathan D. Powell, Vincent K. Tuohy, Daniel J. Cua, Xiaoxia Li

Research output: Contribution to journalArticle

Abstract

Interleukin-1 (IL-1)-mediated signaling in T cells is essential for T helper 17 (Th17) cell differentiation. We showed here that SIGIRR, a negative regulator of IL-1 receptor and Toll-like receptor signaling, was induced during Th17 cell lineage commitment and governed Th17 cell differentiation and expansion through its inhibitory effects on IL-1 signaling. The absence of SIGIRR in T cells resulted in increased Th17 cell polarization in vivo upon myelin oligodendrocyte glycoprotein (MOG35-55) peptide immunization. Recombinant IL-1 promoted a marked increase in the proliferation of SIGIRR-deficient T cells under an in vitro Th17 cell-polarization condition. Importantly, we detected increased IL-1-induced phosphorylation of JNK and mTOR kinase in SIGIRR-deficient Th17 cells compared to wild-type Th17 cells. IL-1-induced proliferation was abolished in mTOR-deficient Th17 cells, indicating the essential role of mTOR activation. Our results demonstrate an important mechanism by which SIGIRR controls Th17 cell expansion and effector function through the IL-1-induced mTOR signaling pathway.

Original languageEnglish (US)
Pages (from-to)54-66
Number of pages13
JournalImmunity
Volume32
Issue number1
DOIs
StatePublished - Jan 29 2010

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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  • Cite this

    Gulen, M. F., Kang, Z., Bulek, K., Youzhong, W., Kim, T. W., Chen, Y., Altuntas, C. Z., Sass Bak-Jensen, K., McGeachy, M. J., Do, J. S., Xiao, H., Delgoffe, G. M., Min, B., Powell, J. D., Tuohy, V. K., Cua, D. J., & Li, X. (2010). The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation. Immunity, 32(1), 54-66. https://doi.org/10.1016/j.immuni.2009.12.003