Defective negative regulation of Toll-like receptor signaling leads to excessive TNF-α in myeloproliferative neoplasm
| العنوان: | Defective negative regulation of Toll-like receptor signaling leads to excessive TNF-α in myeloproliferative neoplasm |
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| المؤلفون: | Michael R. Garbati, Brianna M. Craver, Thanh Kim Nguyen, Hew Yeng Lai, Angela G. Fleischman, Stefan Brooks, Nahideh Haghighi, Sarah J. Morse |
| المصدر: | Blood Advances. 3:122-131 |
| بيانات النشر: | American Society of Hematology, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | medicine.medical_treatment, Clone (cell biology), Monocytes, Proinflammatory cytokine, Mice, medicine, Animals, Humans, Receptors, Interleukin-10, Alleles, Myeloproliferative neoplasm, Toll-like receptor, Myeloproliferative Disorders, Myeloid Neoplasia, Tumor Necrosis Factor-alpha, business.industry, Macrophages, Toll-Like Receptors, food and beverages, Hematology, Janus Kinase 2, medicine.disease, Interleukin 10, Cytokine, Immunology, Cytokines, Tumor necrosis factor alpha, Signal transduction, business, Protein Binding, Signal Transduction |
| الوصف: | Patients with myeloproliferative neoplasms (MPN) have high levels of inflammatory cytokines, some of which drive many of the debilitating constitutional symptoms associated with the disease and may also promote expansion of the neoplastic clone. We report here that monocytes from patients with MPN have defective negative regulation of Toll-like receptor (TLR) signaling that leads to unrestrained production of the inflammatory cytokine tumor necrosis factor α (TNF-α) after TLR activation. Specifically, monocytes of patients with MPN are insensitive to the anti-inflammatory cytokine interleukin 10 (IL-10) that negatively regulates TLR-induced TNF-α production. This inability to respond to IL-10 is a not a direct consequence of JAK2V617F, as the phenotype of persistent TNF-α production is a feature of JAK2V617F and wild-type monocytes alike from JAK2V617F-positive patients. Moreover, persistent TNF-α production was also discovered in the unaffected identical twin of a patient with MPN, suggesting it could be an intrinsic feature of those predisposed to acquire MPN. This work implicates sustained TLR signaling as not only a contributor to the chronic inflammatory state of MPN patients but also a potential predisposition to acquire MPN. |
| تدمد: | 2473-9537 2473-9529 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8bdaee0f15eed02bbb78f4cdcece8dda https://doi.org/10.1182/bloodadvances.2018026450 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8bdaee0f15eed02bbb78f4cdcece8dda |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 24739537 24739529 |
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