These findings point to a defect in the TLR signalling pathways in cutaneous LP. Agonists of TLR7/TLR8 or TLR9 overcame impaired IFN-α secretion in LP, strategically acting as adjuvants to improve the type I response.
Lichen 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-β 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.
Lichen planus (LP) is a chronic inflammatory mucocutaneous disease. The inflammatory status of LP may be related to S100A8 (myeloid-related protein 8; MRP8) activation of cytotoxic cells. The aims of this study were to evaluate S100A8 expression in skin lesions and the in vitro effects of S100A8 on CD8+ T cells and natural killer (NK) cells in LP. Increased levels of S100A8/S100A9 were detected in the skin lesions as well as in the sera of subjects with LP. S100A8 expression induced an increased cytotoxic response by peripheral blood CD8+CD107a+ T cells as well as by NK CD56bright cells in patients with LP. Increased expression of interleukin (IL)-1?, tumour necrosis factor (TNF) and IL-6 in the CD8+ T cells of patients with LP was induced by S100A8, in contrast to the control group that produced IL- 10 and interferon type I genes. These data suggest that, in individuals with LP, S100A8 may exert distinct immunomodulatory and cytotoxicity functions.
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 CD8+CD25+Foxp3+CD127low/− 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.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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0938-1) contains supplementary material, which is available to authorized users.
Lichen planus (LP) is a chronic, mucocutaneous inflammatory disease of an unknown aetiology. The disease has been associated with certain viruses, and the factors such as DAMPs (damage-associated molecular patterns) and PAMPs (pathogen-associated molecular patterns) may also contribute to the inflammatory response in LP. HMGB1 (high mobility group box 1 protein) is one of the major DAMPs that induces inflammation and could trigger LP disease. The present study was aimed to examine TLR4, RAGE and HMGB1 production in epidermis or dermis by immunohistochemistry and the respective expression of these targets in the skin lesions of patients with LP. Moreover, we measured HMGB1 serum levels by ELISA. The results showed similar profile of expression by HMGB1 and TLR4, which are decreased at epidermis and up-regulated at dermis of skin lesions of LP patients that was sustained by intense cellular infiltration. RAGE expression was also increased in dermis of LP. Although there is increased RAGE protein levels, a decreased RAGE transcript levels was detected. Similar HMGB1 serum levels were detected in the LP and control groups. This study demonstrates that HMGB1 and TLR4 could contribute to the inflammatory LP process in skin.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.