Immunity (Cambridge, Mass.), 2017-10, Vol.47 (4), p.710-722.e6
2017
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- Autor(en) / Beteiligte
- Titel
- Epidermal Growth Factor Receptor Expression Licenses Type-2 Helper T Cells to Function in a T Cell Receptor-Independent Fashion
- Ist Teil von
- Immunity (Cambridge, Mass.), 2017-10, Vol.47 (4), p.710-722.e6
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2017
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- Gastro-intestinal helminth infections trigger the release of interleukin-33 (IL-33), which induces type-2 helper T cells (Th2 cells) at the site of infection to produce IL-13, thereby contributing to host resistance in a T cell receptor (TCR)-independent manner. Here, we show that, as a prerequisite for IL-33-induced IL-13 secretion, Th2 cells required the expression of the epidermal growth factor receptor (EGFR) and of its ligand, amphiregulin, for the formation of a signaling complex between T1/ST2 (the IL-33R) and EGFR. This shared signaling complex allowed IL-33 to induce the EGFR-mediated activation of the MAP-kinase signaling pathway and consequently the expression of IL-13. Lack of EGFR expression on T cells abrogated IL-13 expression in infected tissues and impaired host resistance. EGFR expression on Th2 cells was TCR-signaling dependent, and therefore, our data reveal a mechanism by which antigen presentation controls the innate effector function of Th2 cells at the site of inflammation. [Display omitted] •Mice lacking EGFR expression on T cells are more susceptible to worm infections•EGFR forms a complex with T1/ST2, allowing for IL-33 induced IL-13 expression•Amphiregulin-mediated EGFR activation is essential for complex formation with T1/ST2•EGFR expression is induced by TCR engagement and sustained by cytokines, such as TSLP At the site of infection, Th2 cells secrete IL-13 upon exposure to IL-33. Minutti et al. now show that TCR-induced expression of the EGFR and its ligand amphiregulin was essential for IL-33-induced IL-13 secretion, revealing a mechanism whereby antigen-specific activation controls the innate effector function of Th2 cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1074-7613eISSN: 1097-4180DOI: 10.1016/j.immuni.2017.09.013Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5654729
- Format
- –
- Schlagworte
- Amphiregulin, Amphiregulin - immunology, Amphiregulin - metabolism, Animals, Antigen presentation, Antigens, Cell Line, Cells, Cells, Cultured, cytokine signaling, Cytokines, Effector cells, Epidermal growth factor, Epidermal growth factor receptors, ErbB Receptors - genetics, ErbB Receptors - immunology, ErbB Receptors - metabolism, gastro-intestinal helminth infections, Gene Expression - genetics, Gene Expression - immunology, Gene Expression Profiling - methods, HEK293 Cells, Helper cells, Humans, Immune system, Infections, Interleukin 13, Interleukin-13 - genetics, Interleukin-13 - immunology, Interleukin-13 - metabolism, interleukin-33, Interleukin-33 - genetics, Interleukin-33 - immunology, Interleukin-33 - metabolism, Intestine, Licenses, Lymphocytes, Lymphocytes T, MAP Kinase Signaling System - immunology, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Nematospiroides dubius - immunology, Nematospiroides dubius - physiology, Nocardia - immunology, Nocardia - physiology, Nocardia Infections - immunology, Nocardia Infections - metabolism, Nocardia Infections - microbiology, Parasites, Receptors, Antigen, T-Cell - immunology, Receptors, Antigen, T-Cell - metabolism, Regulation, Reverse Transcriptase Polymerase Chain Reaction, Rodents, Signal transduction, Signaling, Strongylida Infections - immunology, Strongylida Infections - metabolism, Strongylida Infections - parasitology, T cell receptors, TCR-independent IL-13 secretion, Th2 Cells - immunology, Th2 Cells - metabolism, Tissues, type-2 helper T cells