ROSANA DOMINGUES
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
Agora exibindo 1 - 2 de 2
- Activation of myeloid dendritic cells, effector cells and regulatory T cells in lichen planus(2016) DOMINGUES, Rosana; CARVALHO, Gabriel Costa de; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiBackground: 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-alpha(+) plasmacytoid DCs (pDCs); TNF-alpha(+) myeloid DCs (mDCs); regulatory T cells (Tregs); and IL-17-, IL-10-, IL-22-, TNF-, and IFN-gamma-secreting T cells were assessed via flow cytometry. Results: The frequencies of regulatory CD4(+) and CD8(+)CD25(+)Foxp3(+)CD127(low/-)T cells and TNF-alpha(+) 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-gamma(+) T cells were found. In the LP group, TLR4 activation induced an increased frequency of CD4(+) IFN-gamma(+) 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.
- Human endogenous retrovirus expression is inversely related with the up-regulation of interferon-inducible genes in the skin of patients with lichen planus(2015) NOGUEIRA, Marcelle Almeida de Sousa; GAVIOLI, Camila Fatima Biancardi; PEREIRA, Natalli Zanete; CARVALHO, Gabriel Costa de; DOMINGUES, Rosana; AOKI, Valeria; SATO, Maria NotomiLichen planus (LP) is a common inflammatory skin disease of unknown etiology. Reports of a common transactivation of quiescent human endogenous retroviruses (HERVs) support the connection of viruses to the disease. HERVs are ancient retroviral sequences in the human genome and their transcription is often deregulated in cancer and autoimmune diseases. We explored the transcriptional activity of HERV sequences as well as the antiviral restriction factor and interferon-inducible genes in the skin from LP patients and healthy control (HC) donors. The study included 13 skin biopsies from patients with LP and 12 controls. Real-time PCR assay identified significant decrease in the HERV-K gag and env mRNA expression levels in LP subjects, when compared to control group. The expressions of HERV-K18 and HERV-W env were also inhibited in the skin of LP patients. We observed a strong correlation between HERV-K gag with other HERV sequences, regardless the down-modulation of transcripts levels in LP group. In contrast, a significant up-regulation of the cytidine deaminase APOBEC 3G (apolipoprotein B mRNA-editing), and the GTPase MxA (Myxovirus resistance A) mRNA expression level was identified in the LP skin specimens. Other transcript expressions, such as the master regulator of type I interferon-dependent immune responses, STING (stimulator of interferon genes) and IRF-7 (interferon regulatory factor 7), IFN-beta and the inflammassome NALP3, had increased levels in LP, when compared to HC group. Our study suggests that interferon-inducible factors, in addition to their role in innate immunity against exogenous pathogens, contribute to the immune control of HERVs. Evaluation of the balance between HERV and interferon-inducible factor expression could possibly contribute to surveillance of inflammatory/malignant status of skin diseases.