IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin
| العنوان: | IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin |
|---|---|
| المؤلفون: | Calum C. Bain, Foo Y. Liew, Ananda S. Mirchandani, Anne-Gaelle Besnard, Neil C. Thomson, Robert J. Salmond |
| المصدر: | The Journal of Allergy and Clinical Immunology |
| بيانات النشر: | Mosby, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | S6K1, Ribosomal protein S6 kinase 1, AHR, Airway hyperresponsiveness, medicine.medical_treatment, Mice, 0302 clinical medicine, PI3K, Phosphoinositide 3-kinase, Immunology and Allergy, TSLP, Thymic stromal lymphopoietin, Cells, Cultured, Mice, Knockout, 0303 health sciences, Immunity, Cellular, Mice, Inbred BALB C, Interleukin-13, TOR Serine-Threonine Kinases, Innate lymphoid cell, rpS6, Ribosomal protein S6, 3. Good health, ICOS, Inducible costimulator, Class Ia Phosphatidylinositol 3-Kinase, TH2, Cytokine, Interleukin 13, mTOR(C1/2), Mammalian target of rapamycin (complex 1/2), Mechanisms of Allergy and Clinical Immunology, medicine.symptom, Signal Transduction, BAL, Bronchoalveolar lavage, WT, Wild-type, APC, Allophycocyanin, Immunology, innate lymphoid cells, P70-S6 Kinase 1, Inflammation, Biology, 03 medical and health sciences, Th2 Cells, ILC, Innate lymphoid cell, medicine, Animals, Humans, PI3K/AKT/mTOR pathway, 030304 developmental biology, mammalian target of rapamycin, Phosphoinositide 3-kinase, rapamycin, Interleukins, Ribosomal Protein S6 Kinases, PE, Phycoerythrin, Pneumonia, Receptors, Interleukin, asthma, Interleukin-33, Interleukin-1 Receptor-Like 1 Protein, Immunity, Innate, TCR, T-cell receptor, Cancer research, biology.protein, IL-33, Cytokine secretion, Interleukin-5, Lin, Lineage-specific marker, 030215 immunology |
| الوصف: | Background: The IL-1 family cytokine IL-33 is involved in the induction of airway inflammation in allergic patients and after viral infection. Several cell types, including CD4 1 TH2 cells and the recently described type 2 innate lymphoid cells (ILCs), are targets for IL-33, yet the mechanisms by which this cytokine modulates their activation are not clear. Objectives: Our goal was to investigate a role for mammalian target of rapamycin (mTOR) signaling in the activation of TH2 and ILC responses and the induction of airway inflammation by IL-33. Methods: We biochemically determined the effect of IL-33 on mTOR activation in TH2 cells and ILCs and examined the effect of this signaling pathway in vivo using a murine model of IL-33‐induced lung inflammation. Results: We found that IL-33 induces mTOR activation through p110d phosphoinositide 3-kinase and that blockade of the mTOR pathway inhibited IL-33‐induced IL-5 and IL-13 production by TH2 cells and ILCs. Furthermore, use of a ribosomal protein S6 kinase 1 inhibitor implicated a role for ribosomal protein S6 kinase 1 in IL-33‐induced mTOR-dependent cytokine production. Intranasal administration of IL-33 to wild-type mice induced airway inflammation, whereas adoptive transfer of wildtype ILCsto IL-33receptor‐deficient(St2 2/2 )mice recapitulated this response. Importantly, coadministration of the mTOR inhibitor rapamycin reduced IL-33‐dependent ILC, macrophage, and eosinophil accumulation; cytokine secretion; and mucus deposition in the airways. Conclusion: These data reveal a hitherto unrecognized role of mTOR signaling in IL-33‐driven, ILC-dependent inflammation in vivo and suggest that manipulation of this pathway might represent a target for therapeutic intervention for airway inflammation. (J Allergy Clin Immunol 2012;130:1159-66.) |
| اللغة: | English |
| تدمد: | 1097-6825 0091-6749 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e5cfddcfe91f7be30f8547bc2fc489c3 http://europepmc.org/articles/PMC3664950 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e5cfddcfe91f7be30f8547bc2fc489c3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10976825 00916749 |
|---|