The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation
| Autor: | Jonathan D. Powell, Zizhen Kang, Katarzyna Bulek, Vincent K. Tuohy, Greg M. Delgoffe, Hui Xiao, Tae Whan Kim, Jeong Su Do, Booki Min, Muhammet F. Gulen, Mandy J. McGeachy, Kristian Sass Bak-Jensen, Cengiz Z. Altuntas, Yi Chen, Daniel J. Cua, Xiaoxia Li, Wan Youzhong |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental Cellular differentiation Immunoblotting Immunology Enzyme-Linked Immunosorbent Assay chemical and pharmacologic phenomena Cell Separation Protein Serine-Threonine Kinases Interleukin-1 receptor Biology Transfection Article Mice T-Lymphocyte Subsets Animals Immunoprecipitation Immunology and Allergy Cell Lineage MOLIMMUNO Receptor PI3K/AKT/mTOR pathway Cell Proliferation Mice Knockout Reverse Transcriptase Polymerase Chain Reaction Cell growth TOR Serine-Threonine Kinases Interleukin-17 RPTOR Intracellular Signaling Peptides and Proteins Receptors Interleukin-1 Cell Differentiation hemic and immune systems T-Lymphocytes Helper-Inducer Flow Cytometry Molecular biology Cell biology Enzyme Activation Infectious Diseases CELLIMMUNO Interleukin 17 Signal transduction Signal Transduction |
| Zdroj: | Immunity. 32:54-66 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2009.12.003 |
| Popis: | SummaryInterleukin-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|