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https://observatorio.fm.usp.br/handle/OPI/17803
Title: | Toll-like receptor agonists partially restore the production of pro-inflammatory cytokines and type I interferon in Sezary syndrome |
Authors: | MANFRERE, Kelly C. G.; TORREALBA, Marina P.; MIYASHIRO, Denis R.; OLIVEIRA, Luanda M. S.; CARVALHO, Gabriel C. de; LIMA, Josenilson F.; BRANCO, Anna Claudia C. C.; PEREIRA, Ntalli Z.; PEREIRA, Juliana; SANCHES JR., Jose A.; SATO, Maria N. |
Citation: | ONCOTARGET, v.7, n.46, p.74592-74601, 2016 |
Abstract: | Sezary syndrome (SS) carries a poor prognosis, and infections represent the most frequent cause of death in SS patients. Toll-like receptors (TLRs) are a family of innate immune receptors that induce protective immune responses against infections. We sought to evaluate the ability of TLR agonists to induce inflammatory cytokine, Th2 cytokine, and type I interferon (IFN-I) production by peripheral blood mononuclear cells (PBMC) of untreated SS patients. We detected impaired IL-6, IL-10 and IL-13 secretion by PBMC induced by the agonists for TLR5, TLR3, TLR7 and TLR9 in SS patients, while it was partially recovered by TLR2/TLR4 and TLR7/8 agonists TNF secretion was restored following stimulation with TLR2/TLR4 agonists. IFN-gamma was scarcely produced upon TLR activation in SS cells, albeit TLR 7/8 (CL097) enhanced their secretion at lower levels than the control group. TLR9 agonist efficiently induced IFN-I in SS patients, although this positive regulation was not observed for other cytokines, in direct contrast to the broad activity of CL097. Among the TLR agonists, TLR4 was able to induce pro-inflammatory, IL-10 and Th2 secretion, while TLR7-8 agonist induced the inflammatory cytokines, IFN-I and IFN-gamma. These findings reveal a dysfunctional cytokine response upon both extracellular and intracellular TLR activation in SS patients, which was partially restored by TLRs agonists. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MCM Artigos e Materiais de Revistas Científicas - FM/MDT Artigos e Materiais de Revistas Científicas - HC/ICHC Artigos e Materiais de Revistas Científicas - LIM/31 Artigos e Materiais de Revistas Científicas - LIM/53 Artigos e Materiais de Revistas Científicas - LIM/56 |
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