Immunity (Cambridge, Mass.), 2010-01, Vol.32 (1), p.54-66
2010
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- Autor(en) / Beteiligte
- Titel
- The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation
- Ist Teil von
- Immunity (Cambridge, Mass.), 2010-01, Vol.32 (1), p.54-66
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 (MOG 35-55) 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. ► SIGIRR is induced during Th17 cell lineage commitment ► SIGIRR suppresses Th17 cell effector function via inhibition of IL-1 signaling ► IL-1-induced proliferation is abolished in mTOR-deficient Th17 cells ► SIGIRR suppresses Th17 cell proliferation via inhibition of mTOR activation
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1074-7613eISSN: 1097-4180DOI: 10.1016/j.immuni.2009.12.003Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3015141
- Format
- –
- Schlagworte
- Animals, Cell Differentiation - immunology, Cell growth, Cell Lineage - immunology, Cell Proliferation, Cell Separation, CELLIMMUNO, Cytokines, Disease, Encephalomyelitis, Autoimmune, Experimental - immunology, Encephalomyelitis, Autoimmune, Experimental - pathology, Enzyme Activation - immunology, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Gene expression, Immune system, Immunoblotting, Immunoprecipitation, Infections, Inflammatory bowel disease, Interleukin-17 - immunology, Interleukin-17 - metabolism, Intracellular Signaling Peptides and Proteins - immunology, Intracellular Signaling Peptides and Proteins - metabolism, Kinases, Mice, Mice, Knockout, MOLIMMUNO, Pathogenesis, Protein-Serine-Threonine Kinases - immunology, Protein-Serine-Threonine Kinases - metabolism, Receptors, Interleukin-1 - immunology, Receptors, Interleukin-1 - metabolism, Reverse Transcriptase Polymerase Chain Reaction, Rodents, Signal Transduction - immunology, T-Lymphocyte Subsets - cytology, T-Lymphocyte Subsets - immunology, T-Lymphocyte Subsets - metabolism, T-Lymphocytes, Helper-Inducer - cytology, T-Lymphocytes, Helper-Inducer - immunology, T-Lymphocytes, Helper-Inducer - metabolism, TOR Serine-Threonine Kinases, Transfection