title: Toll-like receptor agonists partially restore the production of pro-inflammatory cytokines and type I interferon in Sézary syndrome.
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: Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.
authors: Kelly C G
authors: KC
authors: Manfrere
authors: Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.
authors: Marina P
authors: MP
authors: Torrealba
authors: Department of Dermatology, Cutaneous Lymphoma Clinic, Hospital das Clínicas, University of São Paulo, Medical School, Brazil.
authors: Denis R
authors: DR
authors: Miyashiro
authors: Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.
authors: Luanda M S
authors: LM
authors: Oliveira
authors: Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.
authors: Gabriel C
authors: GC
authors: de Carvalho
authors: Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.
authors: Josenilson F
authors: JF
authors: Lima
authors: Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.
authors: Anna Claudia C C
authors: AC
authors: Branco
authors: Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.
authors: Nátalli Z
authors: NZ
authors: Pereira
authors: Department of Hematology, University of São Paulo Medical School, Brazil.
authors: Juliana
authors: J
authors: Pereira
authors: Department of Dermatology, Cutaneous Lymphoma Clinic, Hospital das Clínicas, University of São Paulo, Medical School, Brazil.
authors: José A
authors: JA
authors: Sanches
authors: Department of Dermatology, Laboratory of Medical Investigation (LIM 56), Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, Brazil.
authors: Maria N
authors: MN
authors: Sato
mesh_terms: D000368:Aged; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D007370:Interferon Type I / Q000097:blood / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012751:Sezary Syndrome / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007370:Interferon Type I; D051193:Toll-Like Receptors
keywords: Immune response; Immunity; Immunology and Microbiology Section; Toll-like receptor agonists; cytokines; innate immunity; type I interferon; Sézary syndrome