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Toll-like receptor agonists partially restore the production of pro-inflammatory cytokines and type I interferon in Sézary syndrome.
Oncotarget 2016; 7(46):74592-74601O

Abstract

Sézary 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-γ 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-γ. These findings reveal a dysfunctional cytokine response upon both extracellular and intracellular TLR activation in SS patients, which was partially restored by TLRs agonists.

Authors+Show Affiliations

Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.Department of Dermatology, Cutaneous Lymphoma Clinic, Hospital das Clínicas, University of São Paulo, Medical School, Brazil.Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.Department of Hematology, University of São Paulo Medical School, Brazil.Department of Dermatology, Cutaneous Lymphoma Clinic, Hospital das Clínicas, University of São Paulo, Medical School, Brazil.Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27780938

Citation

Manfrere, Kelly C G., et al. "Toll-like Receptor Agonists Partially Restore the Production of Pro-inflammatory Cytokines and Type I Interferon in Sézary Syndrome." Oncotarget, vol. 7, no. 46, 2016, pp. 74592-74601.
Manfrere KC, Torrealba MP, Miyashiro DR, et al. Toll-like receptor agonists partially restore the production of pro-inflammatory cytokines and type I interferon in Sézary syndrome. Oncotarget. 2016;7(46):74592-74601.
Manfrere, K. C., Torrealba, M. P., Miyashiro, D. R., Oliveira, L. M., de Carvalho, G. C., Lima, J. F., ... Sato, M. N. (2016). Toll-like receptor agonists partially restore the production of pro-inflammatory cytokines and type I interferon in Sézary syndrome. Oncotarget, 7(46), pp. 74592-74601. doi:10.18632/oncotarget.12816.
Manfrere KC, et al. Toll-like Receptor Agonists Partially Restore the Production of Pro-inflammatory Cytokines and Type I Interferon in Sézary Syndrome. Oncotarget. 2016 11 15;7(46):74592-74601. PubMed PMID: 27780938.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Toll-like receptor agonists partially restore the production of pro-inflammatory cytokines and type I interferon in Sézary syndrome. AU - Manfrere,Kelly C G, AU - Torrealba,Marina P, AU - Miyashiro,Denis R, AU - Oliveira,Luanda M S, AU - de Carvalho,Gabriel C, AU - Lima,Josenilson F, AU - Branco,Anna Claudia C C, AU - Pereira,Nátalli Z, AU - Pereira,Juliana, AU - Sanches,José A,Jr AU - Sato,Maria N, PY - 2016/07/28/received PY - 2016/10/14/accepted PY - 2016/10/27/pubmed PY - 2018/2/9/medline PY - 2016/10/27/entrez KW - Immune response KW - Immunity KW - Immunology and Microbiology Section KW - Toll-like receptor agonists KW - cytokines KW - innate immunity KW - type I interferon KW - Sézary syndrome SP - 74592 EP - 74601 JF - Oncotarget JO - Oncotarget VL - 7 IS - 46 N2 - Sézary 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-γ 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-γ. These findings reveal a dysfunctional cytokine response upon both extracellular and intracellular TLR activation in SS patients, which was partially restored by TLRs agonists. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/27780938/Toll_like_receptor_agonists_partially_restore_the_production_of_pro_inflammatory_cytokines_and_type_I_interferon_in_Sézary_syndrome_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=12816 DB - PRIME DP - Unbound Medicine ER -