| Full text | |
| Author(s): Show less - |
Manfrere, Kelly C. G.
;
Torrealba, Marina P.
;
Miyashiro, Denis R.
;
Oliveira, Luanda M. S.
;
de Carvalho, Gabriel C.
;
Lima, Josenilson F.
;
Branco, Anna Claudia C. C.
;
Pereira, Ntalli Z.
;
Pereira, Juliana
;
Sanches, Jr., Jose A.
;
Sato, Maria N.
Total Authors: 11
|
| Document type: | Journal article |
| Source: | ONCOTARGET; v. 7, n. 46, p. 74592-74601, NOV 15 2016. |
| Web of Science Citations: | 4 |
| 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. (AU) | |
| FAPESP's process: | 14/04865-9 - Activation of cytotoxic response mediated by polyfunctional natural killer cells and t CD8+ cells induced by Toll-like-receptors agonists in the mycosis fungoides and Sézary syndrome |
| Grantee: | José Antonio Sanches Junior |
| Support Opportunities: | Regular Research Grants |