Defective negative regulation of Toll-like receptor signaling leads to excessive TNF-α in myeloproliferative neoplasm.

ABSTRACT: 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 JAK2 ^V617F , as the phenotype of persist

SUBMITTER: Lai HY 

PROVIDER: S-EPMC6341195 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature