Evaluation of the Th17 pathway in psoriasis and geographic tongue

Abstract Background: Psoriasis is a skin-articular disease with unclear etiopathogenesis. It has been suggested that the disease is immune-mediated by T-lymphocytes, predominantly Th17 cells. Similar to psoriasis, geographic tongue is an inflammatory disease with participation of Th17 cells and direct correlation with psoriasis. Objective: To investigate and compare the inflammatory responses and the Th17 pathway in psoriasis and geographic tongue. Methods: This was a cross-sectional study with 46 participants that were categorized into three groups: (A) patients with psoriasis vulgaris; (B) patients with geographic tongue and psoriasis; (C) patients with geographic tongue without psoriasis. All patients underwent physical examination, and a skin and oral biopsy for histopathological examination and immunohistochemical analysis with anti-IL6, anti-IL17, and anti-IL23 antibodies. Results: Histological analysis of all lesions showed mononuclear inflammatory infiltrate. However, moderate intensity was prevalent for the patients with geographic tongue and psoriasis and geographic tongue groups. Immunopositivity for the antibodies anti-IL6, anti-IL17, and anti-IL23 revealed cytoplasmic staining, mainly basal and parabasal, in both psoriasis and geographic tongue. Regarding IL-6, in patients with geographic tongue and psoriasis cases the staining was stronger than in patients with geographic tongue without psoriasis cases. IL-17 evidenced more pronounced and extensive staining when compared to the other analyzed interleukins. IL-23 presented similar immunopositivity for both geographic tongue and psoriasis, demonstrating that the neutrophils recruited into the epithelium were stained. Study limitation: This study was limited by the number of cases. Conclusion: The inflammatory process and immunostaining of IL-6, IL-17, and IL-23 were similar in geographic tongue and psoriasis, suggesting the existence of a type of geographic tongue that represents an oral manifestation of psoriasis.

Evaluation of the cervicovaginal environment in asymptomatic Human T-cell lymphotropic virus type 1 infected women

ABSTRACT Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) is sexually transmitted and causes persistent infection. This virus induces activation of the immune system and production of inflammatory cytokines. This study aimed to assess the cytokine profile and cytopathological findings in the cervicovaginal fluid of asymptomatic HTLV-1-infected women. Methods: HTLV-1-infected and uninfected women were selected at the Centro de Atendimento ao Portador de HTLV in Salvador-Brazil. None of the included HTLV-1-infected women reported any HTLV-1-associated diseases. All volunteers underwent gynecological examination to collect cervicovaginal fluid. Cytokine quantification was performed using the Cytometric Bead Array (CBA) Human Th1/Th2/Th17 kit. Light microscopy was used to evaluate cervicovaginal cytopathology. In addition, proviral load in cervicovaginal fluid and peripheral blood was measured by real-time quantitative polymerase chain reaction. Results: 112 women (63 HTLV-1-infected and 49 uninfected) were evaluated. No differences were found with respect to cytopathological cervicovaginal findings between the groups. IL-2, TNF, IL-4, IL-10, and IL-17 levels were significantly higher in cervicovaginal fluid of the HTLV-1-infected women than in uninfected women (p < 0.05). Conversely, IFN-γ was found to be lower in the HTLV-1-infected women (p < 0.001) compared to uninfected individuals. Cervicovaginal proviral load was detectable in 53% of the HTLV-1-infected women and was found to be consistently lower than the proviral load in peripheral blood. Conclusions: HTLV-1 infection induces immune activation in cervicovaginal environment, characterized by elevated concentrations of Th1, Th2, and IL17 in the cervicovaginal fluid.

Imbalance of γδT17/γδTreg cells in the pathogenesis of allergic asthma induced by ovalbumin

We aimed to explore the imbalance between the T helper 17 γδT cells (γδT17) and the regulatory γδT cells (γδTreg) in asthmatic mice. Male Balb/c mice were randomly divided into the normal control group and the asthmatic model group. The asthmatic model group mice were intraperitoneally injected with the mixture of ovalbumin (OVA)/Al(OH)3 and then activated by exposure of the animals to OVA atomization. Airway hyperresponsiveness (AHR) was determined by a non-invasive lung function machine. Hematoxylin and eosin and Alcian blue-periodic acid Schiff staining were done for histopathological analysis. Interleukin (IL)-17 and IL-35 levels in bronchoalveolar lavage fluid were detected by ELISA. The percentage of IL-17+ γδT cells and Foxp3+ γδT cells in spleen cells suspension were detected and the transcription levels of RORγt and Foxp3 in the lung tissue were determined. Compared with the normal control, the severity of airway inflammation and AHR were higher in the asthmatic mice. Furthermore, mice in the asthmatic group displayed significant increases of IL-17+ γδT cells, expression of IL-17A, and RORγt, whereas control mice displayed marked decreases of Foxp3+ γδT cells, expression of IL-35, and transcription factor Foxp3. In addition, the mRNA expression of RORγt was positively correlated with the percentage of IL-17+γδT cells, and the mRNA level of Foxp3 was positively correlated with the percentage of Foxp3+ γδT cells. The imbalance of γδT17/γδTreg in the asthmatic mice may contribute to the pathogenesis of OVA-induced asthma.

Interleukin 17 A, hepatosplenic mansonic schistosomiasis and atherosclerosis / Interleucina 17 A, esquistossomose mansônica forma hepatoesplênica e aterosclerose

Objective: To evaluate serum concentrations of interleukin 17A (IL17A) in mansonic schistosomiasis patients, while the secondary objectives were to detect atherosclerotic disease, and to evaluate serum concentrations of interleukin 22 (IL22). Methods: This study included 30 patients with an established diagnosis of hepatosplenic mansonic schistosomiasis and 10 healthy volunteers. Comparative analyses of IL17A and IL22 concentrations were performed on the sera of patients and controls. Atherosclerosis was evaluated through carotid artery intima-media thickness measurement of the first 15 patients enrolled. Results: There were no differences in IL17 A concentrations (15.63±0.00pg/mL vs. 15.63±0.00pg/mL; p=1) and in IL22 concentrations (7.81±0.00pg/mL vs. 7.81±0.00pg/ mL, p=1) between patients and controls. The overall mean of intima-media thickness was 0.7±0.2mm. Conclusions: Serum concentrations of IL17A and IL22 were equal between patients and controls (undetectable or low concentrations). No patients had atheroma.

Objetivo: Avaliar as concentrações séricas de interleucina 17A (IL17A) em pacientes com esquistossomose mansônica, enquanto os objetivos secundários foram detectar a doença aterosclerótica e avaliar as concentrações séricas de interleucina 22 (IL22). Métodos: Este estudo incluiu 30 pacientes com diagnóstico estabelecido de esquistossomose mansônica em sua forma hepatoesplênica e 10 voluntários saudáveis. Análises comparativas de concentrações de IL17A e IL22 foram realizadas em soros de pacientes e controles. A aterosclerose foi avaliada pela medida do complexo íntima-média dos primeiros 15 pacientes recrutados. Resultados: Não houve diferença nas concentrações de IL17A (15,63±0,00pg/mL vs. 15,63±0,00pg/mL; p=1) e nas concentrações IL 2 (7,81±0,00pg/mL vs. 7,81±0,00pg/mL; p=1) entre os pacientes e controles. A média geral da espessura da camada média da íntima foi de 0,7±0,2mm. Conclusões: As concentrações séricas de IL17A e IL22 foram iguais entre pacientes e controles (concentrações indetectáveis ou baixa). Nenhum dos pacientes apresentou ateroma.

Follicular helper T cell in immunity and autoimmunity

The traditional concept that effector T helper (Th) responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17) and the follicular helper T cells (Tfh). These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R), the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases.

Genetic controls of Th17 cell differentiation and plasticity

CD4+ T lymphocytes play a major role in regulation of adaptive immunity. Upon activation, naive T cells differentiate into different functional subsets. In addition to the classical Th1 and Th2 cells, several novel effector T cell subsets have been recently identified, including Th17 cells. There has been rapid progress in characterizing the development and function of Th17 cells. Here I summarize and discuss on the genetic controls of their differentiation and emerging evidence on their plasticity. This information may benefit understanding and treating immune diseases.

Sequential evolution of IL-17 responses in the early period of allograft rejection

In addition to CD4+CD25+Foxp3+ regulatory T (T(reg)) cells which protect against autoimmune tissue injury, IL-17-producing CD4+ T (Th17) cells have been recently described and shown to play a crucial role in autoimmune injury. It appears that there is a reciprocal developmental pathway between Th17 and T(reg) cells. Although IL-17 is known to be associated with allograft rejection, the cellular source of IL-17 and the nature of Th17 in the context of allograft rejection remain unknown. In the current study, the dynamics of T(reg) and IL-17-producing cells after syngeneic and allogeneic transplantation were examined using a wild-type murine cardiac transplantation model. Ly6G+ cells were found to produce IL-17 during the early postoperative period and CD8+ as well as CD4+ T cells were also found to produce IL-17 during alloimmune response. Graft-infiltrating Ly6G+, CD4+, and even CD8+ cells were found to express IL-17 highly compared to those in spleen. Although the frequencies of Th17 and T(reg) were found to gradually increase in both syngeneic and allogeneic recipients, Th17/T(reg) ratios were significantly higher in recipients with allograft rejection than in syngeneic recipients. In conclusion, IL-17 is produced by neutrophils during the early postoperative period and subsequently by Th17 and CD8+ T cells during allograft rejection. Th17/T(reg) imbalance is associated with the development of allograft rejection. This study would provide basic information on Th17 biology for future investigation in the field of transplantation.