The dysfunctional innate immune response triggered by Toll-like receptor activation is restored by TLR7/TLR8 and TLR9 ligands in cutaneous lichen planus

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorDOMINGUES, R.
dc.contributor.authorCARVALHO, G. Costa de
dc.contributor.authorOLIVEIRA, L. M. da Silva
dc.contributor.authorTANIGUCHI, E. Futata
dc.contributor.authorZIMBRES, J. M.
dc.contributor.authorAOKI, V.
dc.contributor.authorDUARTE, A. J. da Silva
dc.contributor.authorSATO, M. N.
dc.date.accessioned2015-07-01T20:19:54Z
dc.date.available2015-07-01T20:19:54Z
dc.date.issued2015
dc.description.abstractBackgroundLichen planus (LP) is a chronic inflammatory mucocutaneous disease. Toll-like receptors (TLRs) bind numerous exogenous and endogenous antigens by recognizing conserved pathogen-associated molecular patterns (PAMPs) and have the ability to induce the production of proinflammatory cytokines. Therefore, alterations in innate immunity could explain the inflammation and T-cell autoreactivity leading to the development of LP disease. ObjectivesTo evaluate how the host innate immune response to PAMPs is affected by cutaneous LP, primarily by using TLR agonists to induce proinflammatory cytokine secretion from peripheral blood mononuclear cells (PBMCs). MethodsPBMCs from patients with LP and healthy control (HC) individuals were stimulated with agonists of TLR2/TLR1 (pam3csk4), TLR3 [poly(I:C)-RIG], TLR4 (lipopolysaccharide), TLR5 (flagellin), TLR7 (imiquimod), TLR7/TLR8 (CL097) and TLR9 (CpG). Cytokines from culture supernatants (n=10-12) andserum chemokines and cytokines (n=22-24) were measured using flow cytometry. ResultsActivation through the TLR2, TLR4 and TLR5 pathways induced increased tumour necrosis factor (TNF)- secretion by PBMCs from individuals with LP compared with the HC group. In contrast, activation through TLR3 and TLR7 was impaired in the LP group, leading to decreased TNF- secretion. Moreover, intracellular TLR activation resulted in reduced interleukin (IL)-1 and IL-6 secretion. Notably, individuals with LP became responders on stimulation with TLR7/TLR8 and TLR9 agonists; responses were measured as increases in interferon (IFN)- production. Detectable TNF- and high CXCL9 and CXCL10 serum levels were observed in patients with LP, suggesting their potential use as markers of the inflammatory status in LP. ConclusionsThese findings point to a defect in the TLR signalling pathways in cutaneous LP. Agonists of TLR7/TLR8 or TLR9 overcame impaired IFN- secretion in LP, strategically acting as adjuvants to improve the type I response.
dc.description.indexMEDLINE
dc.identifier.citationBRITISH JOURNAL OF DERMATOLOGY, v.172, n.1, p.48-55, 2015
dc.identifier.doi10.1111/bjd.13214
dc.identifier.eissn1365-2133
dc.identifier.issn0007-0963
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/9341
dc.language.isoeng
dc.publisherWILEY-BLACKWELL
dc.relation.ispartofBritish Journal of Dermatology
dc.rightsrestrictedAccess
dc.rights.holderCopyright WILEY-BLACKWELL
dc.subject.otherhepatitis-c virus
dc.subject.otherplasmacytoid dendritic cells
dc.subject.othernecrosis-factor-alpha
dc.subject.otherautoimmune-diseases
dc.subject.otherepithelial-cells
dc.subject.otherexpression
dc.subject.otherserum
dc.subject.otherinfection
dc.subject.otherimmunotherapy
dc.subject.otherinflammasomes
dc.subject.wosDermatology
dc.titleThe dysfunctional innate immune response triggered by Toll-like receptor activation is restored by TLR7/TLR8 and TLR9 ligands in cutaneous lichen planus
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalTANIGUCHI, E. Futata:Univ Sao Paulo, Sch Med, Dept Dermatol, Lab Dermatol & Immunodeficiencies,LIM 56, BR-05403000 Sao Paulo, Brazil
hcfmusp.citation.scopus19
hcfmusp.contributor.author-fmusphcROSANA DOMINGUES
hcfmusp.contributor.author-fmusphcGABRIEL COSTA DE CARVALHO
hcfmusp.contributor.author-fmusphcLUANDA MARA DA SILVA OLIVEIRA
hcfmusp.contributor.author-fmusphcJULIANA MENEZES ZIMBRES
hcfmusp.contributor.author-fmusphcVALERIA AOKI
hcfmusp.contributor.author-fmusphcALBERTO JOSE DA SILVA DUARTE
hcfmusp.contributor.author-fmusphcMARIA NOTOMI SATO
hcfmusp.description.beginpage48
hcfmusp.description.endpage55
hcfmusp.description.issue1
hcfmusp.description.volume172
hcfmusp.origemWOS
hcfmusp.origem.pubmed24976336
hcfmusp.origem.scopus2-s2.0-84920713537
hcfmusp.origem.wosWOS:000347726500011
hcfmusp.publisher.cityHOBOKEN
hcfmusp.publisher.countryUSA
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