Activation of myeloid dendritic cells, effector cells and regulatory T cells in lichen planus.
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.



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.



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.



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.
Laboratory 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.
Rosana
R
Domingues
Laboratory 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.
Gabriel Costa
GC
de Carvalho
Dermatological Outpatient Clinic, Hospital das Clínicas, Medical School of the University of São Paulo, São Paulo, Brazil.
Valéria
V
Aoki
Laboratory 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.
Alberto José
AJ
da Silva Duarte
Laboratory 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. marisato@usp.br.
Maria Notomi
MN
Sato
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D008010:Lichen Planus / Q000097:blood / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D016207:Cytokines; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha
Dendritic cells; Lichen planus; Polyfunctional T cells; Regulatory T cells; Toll-like receptor