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Activation of myeloid dendritic cells, effector cells and regulatory T cells in lichen planus
Rosana Domingues1, Gabriel Costa de Carvalho1, Valéria Aoki2
1Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, University of São Paulo, Institut of Tropical Medicine of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 500, 3rd floor 24, São Paulo, 05403-000, Brazil.
Background:
Lichen 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.
Methods:
Peripheral 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.
Results:
The frequencies of regulatory CD4(+) and CD8(+)CD25(+)Foxp3(+)CD127(low/-) 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 CD4(+)IL-10(+) T cells and CD8(+)IL-22(+) or IFN-γ(+)T cells were found. In the LP group, TLR4 activation induced an increased frequency of CD4(+)IFN-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.
Conclusions:
TLR-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.
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