Activation of myeloid dendritic cells, effector cells and regulatory T cells in lichen planusReport as inadecuate




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Journal of Translational Medicine

, 14:171

Immunobiology and immunotherapy

Abstract

BackgroundLichen planus LP is a chronic mucocutaneous inflammatory disease. Evaluating the balance between regulatory T cells and effector T cells could be useful for monitoring the proinflammatory profile of LP. Therefore, this study aimed to assess populations of dendritic cells DCs and regulatory and effector T cells in peripheral blood samples collected from patients with LP to evaluate the polyfunctionality of T cells upon toll-like receptor TLR activation.

MethodsPeripheral blood mononuclear cells collected from 18 patients with LP and 22 healthy control subjects were stimulated with agonists of TLR4, TLR7, TLR7-TLR8 or TLR9. Frequencies of circulating IFN-α plasmacytoid DCs pDCs; TNF-α myeloid DCs mDCs; regulatory T cells Tregs; and IL-17-, IL-10-, IL-22-, TNF-, and IFN-γ-secreting T cells were assessed via flow cytometry.

ResultsThe frequencies of regulatory CD4 and CD8CD25Foxp3CD127 T cells and TNF-α mDCs were induced following activation with TLR4, TLR7 and TLR8 agonists in the LP group. Moreover, increased baseline frequencies of CD4IL-10 T cells and CD8IL-22 or IFN-γT cells were found. In the LP group, TLR4 activation induced an increased frequency of CD4IFN-γ T cells, while TLR7-8 and staphylococcal enterotoxin B SEB activation induced an increased frequency of CD8 IL-22 T cells. An increased frequency of polyfunctional CD4 T cells that simultaneously secreted 3 of the evaluated cytokines not including IL-10 was verified upon TLR7-8-9 activation, while polyfunctional CD8 T cells were already detectable at baseline.

ConclusionsTLR-mediated activation of the innate immune response induced the production of proinflammatory mDCs, Tregs and polyfunctional T cells in patients with LP. Therefore, TLR activation has an adjuvant role in inducing both innate and adaptive immune responses.

KeywordsLichen planus Toll-like receptor Dendritic cells Regulatory T cells Polyfunctional T cells AbbreviationsLPlichen planus

DCdendritic cells

TLRtoll-like receptors

pDCplasmacytoid dendritic cells

mDCmyeloid dendritic cells

IFN-αinterferon alpha

TNF-αtumour necrosis factor alpha

TregsT regulatory cells

ILinterleukin

TNFtumour necrosis factor

PBMCsperipheral blood mononuclear cells

tTregthymic T regulatory cells

pTregperipherally induced T regulatory cells

OLPoral lichen planus

PMAphorbol myristate acetate

ThT helper

LPSlipopolysaccharide

SEBenterotoxin B from Staphylococcus aureus

HCVhepatitis C virus

TCRT cell receptor

AIDSacquired immunodeficiency syndrome

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-016-0938-1 contains supplementary material, which is available to authorized users.

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Author: Rosana Domingues - Gabriel Costa de Carvalho - Valéria Aoki - Alberto José da Silva Duarte - Maria Notomi Sato

Source: https://link.springer.com/







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