Toll-like receptor agonists partially restore the production of pro-inflammatory cytokines and type I interferon in Sezary syndrome

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author MANFRERE, Kelly C. G. FMUSP-HC
TORREALBA, Marina P. FMUSP-HC
MIYASHIRO, Denis R. FMUSP-HC
OLIVEIRA, Luanda M. S. FMUSP-HC
CARVALHO, Gabriel C. de FMUSP-HC
LIMA, Josenilson F. FMUSP-HC
BRANCO, Anna Claudia C. C. FMUSP-HC
PEREIRA, Ntalli Z.
PEREIRA, Juliana FMUSP-HC
SANCHES JR., Jose A. FMUSP-HC
SATO, Maria N. FMUSP-HC
dc.date.issued 2016
dc.identifier.citation ONCOTARGET, v.7, n.46, p.74592-74601, 2016
dc.identifier.issn 1949-2553
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/17803
dc.description.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.
dc.description.sponsorship · Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2014/04865-9]
· Fundo de Apoio a Dermatologia de Sao Paulo [018-2015]
· Laboratorio de Investigacao Medica, Unidade 56 do Hospital das Clinicas da Faculdade de Medicina de Sao Paulo
dc.language.iso eng
dc.publisher IMPACT JOURNALS LLC
dc.relation.ispartof Oncotarget
dc.rights openAccess
dc.subject Sezary syndrome; innate immunity; Toll-like receptor agonists; cytokines; type I interferon; Immunology and Microbiology Section; Immune response; Immunity
dc.subject.other t-cell lymphoma; single-stranded rna; mycosis-fungoides; immune-response; dendritic cells; immunopathogenesis; recognition; therapy; pathway; cancer
dc.title Toll-like receptor agonists partially restore the production of pro-inflammatory cytokines and type I interferon in Sezary syndrome
dc.type article
dc.rights.holder Copyright IMPACT JOURNALS LLC
dc.description.group LIM/56
dc.description.group LIM/31
dc.description.group LIM/53
dc.identifier.doi 10.18632/oncotarget.12816
dc.identifier.pmid 27780938
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author MANFRERE, Kelly C. G.:FM:
hcfmusp.author TORREALBA, Marina P.:FM:
hcfmusp.author MIYASHIRO, Denis R.:HC:ICHC
hcfmusp.author OLIVEIRA, Luanda M. S.:FM:
hcfmusp.author CARVALHO, Gabriel C. de:FM:
hcfmusp.author LIMA, Josenilson F.:FM:
hcfmusp.author BRANCO, Anna Claudia C. C.:HC:LIM/56
hcfmusp.author PEREIRA, Juliana:FM:MCM
hcfmusp.author SANCHES JR., Jose A.:FM:MDT
hcfmusp.author SATO, Maria N.:FM:MDT
hcfmusp.author.external · PEREIRA, Ntalli Z.:Univ Sao Paulo, Sch Med, Dept Dermatol, Lab Med Invest,LIM 56,Trop Med Inst Sao Paulo, BR-05508 Sao Paulo, Brazil
hcfmusp.origem.id WOS:000389632800015
hcfmusp.origem.id 2-s2.0-84996798832
hcfmusp.publisher.city ALBANY
hcfmusp.publisher.country USA
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dc.description.index MEDLINE
hcfmusp.citation.scopus 4
hcfmusp.citation.wos 4
hcfmusp.affiliation.country Brasil


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