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.

CD19+ B cell subsets in the peripheral blood and skin lesions of psoriasis patients and their correlations with disease severity

T lymphocytes are important in the pathogenesis of psoriasis, and increasing evidence indicates that B cells also play an important role. The mechanisms of action, however, remain unclear. We evaluated the ratios of CD19+ B cells in peripheral blood mononuclear cells (PBMCs) from 157 patients with psoriasis (65 patients with psoriasis vulgaris, 32 patients with erythrodermic psoriasis, 30 patients with arthropathic psoriasis, and 30 patients with pustular psoriasis) and 35 healthy controls (HCs). Ratios of CD19+ B cells in skin lesions were compared with non-lesions in 7 erythrodermic psoriasis patients. The Psoriasis Area Severity Index (PASI) was used to measure disease severity. CD19+ B cell ratios in PBMCs from psoriasis vulgaris (at both the active and stationary stage) and arthropathic psoriasis patients were higher compared with HCs (P<0.01), but ratios were lower in erythrodermic and pustular psoriasis patients (P<0.01). CD19+ B cell ratios in erythrodermic psoriasis skin lesions were higher than in non-lesion areas (P<0.001). Different subsets of CD19+CD40+, CD19+CD44+, CD19+CD80+, CD19+CD86+, CD19+CD11b+, and CD19+HLA-DR+ B cells in PBMCs were observed in different psoriasis clinical subtypes. PASI scores were positively correlated with CD19+ B cell ratios in psoriasis vulgaris and arthropathic psoriasis cases (r=0.871 and r=0.692, respectively, P<0.01), but were negatively correlated in pustular psoriasis (r=-0.569, P<0.01). The results indicated that similar to T cells, B cells activation may also play important roles in different pathological stages of psoriasis.

Pathophysiology of psoriasis.

Psoriasis is a chronic inflammatory papulosquamous disease characterized by multiple remissions and relapses. For long, it was believed to be primarily a disorder of keratinization. However, the successful use of traditional immunosupressants and newer immunomodulatory agents in the treatment of psoriasis led to the belief that psoriasis is primarily a disease of Th1 cell immune dysregulation. Recent developments have brought up several new findings such as the role of Th17 cells and evidence of skin barrier dsysfunction in psoriasis, akin to atopic dermatitis. The present review aims to focus on these new developments and explain the pathogenesis of psoriasis on the basis of currently available information.

Pathophysiology of psoriasis.

Psoriasis is a chronic inflammatory papulosquamous disease characterized by multiple remissions and relapses. For long, it was believed to be primarily a disorder of keratinization. However, the successful use of traditional immunosupressants and newer immunomodulatory agents in the treatment of psoriasis led to the belief that psoriasis is primarily a disease of Th1 cell immune dysregulation. Recent developments have brought up several new findings such as the role of Th17 cells and evidence of skin barrier dsysfunction in psoriasis, akin to atopic dermatitis. The present review aims to focus on these new developments and explain the pathogenesis of psoriasis on the basis of currently available information.

Inmunopatogenia de la psoriasis. Impacto en las manifestaciones clínicas y el tratamiento de la enfermedad / Immunopathogenesis of psoriasis. Impact on clinical manifestations and its treatment

La psoriasis es una enfermedad inflamatoria crónica de la piel mediada por células T que afecta a individuos con predisposición genética y presenta varios subtipos clínicos. Se caracteriza por la presencia de placas eritematosas bien definidas, escamosas y de bordes irregulares, que afectan fundamentalmente las regiones de los codos, las rodillas, el cuero cabelludo y el tronco. El alelo HLA-Cw6 del sistema principal de histocompatibilidad está relacionado con la presencia y severidad de la enfermedad. Desde el punto de vista fisiopatogénico, la psoriasis es una enfermedad inmune de tipo Th1, en la que es fundamental el eje IL-23/Th17. Las células Th17 producen las citocinas proinflamatorias (IL-17A, IL-17F, IL-22 e IL-26) que activan los queratinocitos y causan hiperproliferación y mayor producción de citocinas proinflamatorias y péptidos antimicrobianos, los que a su vez reclutan y activan otras células inmunes de la piel inflamada. Se produce así una amplificación de la respuesta inflamatoria que conduce a las manifestaciones clínicas de la enfermedad. El tratamiento de la psoriasis incluye agentes antiinflamatorios tópicos, fototerapia, inmunosupresores sistémicos y agentes biológicos, entre los que se encuentran las proteínas de fusión, los inhibidores del factor de necrosis tumoral alfa y los inhibidores de las interleucinas 12 y 23

Psoriasis is a T cell-mediated chronic inflammatory disease of the skin. It affects genetically predisposed individuals and presents several subtypes. It is characterized by the presence of well-defined erythematous, scaly, irregular border plaque or lesions, affecting mainly the elbows, knees, scalp, and trunk. The HLA-Cw6 allele of major histocompatibility system is related to the presence and severity of this disease. From the physiopathogenic viewpoint, psoriasis is a Th1-type immune disease in which the axle IL-23/Th17 is fundamental. Th17 cells produce proinflammatory cytokines (IL-17A, IL-17F, IL-22 and IL-26) which activate keratinocytes and cause hyperproliferation and increased production of proinflammatory cytokines and antimicrobial peptides. The latter, in turn, recruit and activate other immune cells of swollen skin. There is thus an amplification of the inflammatory response that leads to clinical manifestations of this disease. The treatment of psoriasis includes topical antiinflammatory agents, phototherapy and systemic immunosuppressive biological agents, including those which are fusion proteins, inhibitors of alpha tumor factor necrosis, and interleukin inhibitors 12 and 23

Tumor necrosis factor-alpha and the cytokine network in psoriasis / Fator de necrose tumoral-alfa e a rede de citocinas na psoriase

New molecular methods of research have greatly expanded the knowledge about the role of cytokines in several diseases, including psoriasis. The work orchestrated by these peptides is essential for the communication between resident inflammatory cells (keratinocytes and endothelial cells) and infiltrating cells (neutrophils, lymphocytes, Langerhans cells). This is a complex network due to redundancy, synergism and, sometimes, the antagonism of cytokines, which prevents full understanding of the pathogenesis of the disease. Currently, it seems premature to try to establish a main actor, but TNFalpha participates in all stages of psoriatic plaque development, as we shall see.

A introdução de novos métodos moleculares de investigação ampliou muito o conhecimento sobre o papel das citocinas em diversas doenças, entre elas a psoríase. O trabalho orquestrado desses polipeptídeos é fundamental na comunicação entre as células inflamatórias residentes (queratinócitos e células endoteliais) e infiltrantes (neutrófilos, linfócitos, células de Langerhans). Trata-se de uma rede complexa devido à redundância, ao sinergismo e, por vezes, ao antagonismo das citocinas, o que dificulta a compreensão da fisiopatogenia da doença a partir de um mecanismo linear. No momento atual, parece precoce tentar estabelecer um regente, mas o TNF-alfa se destaca em todos os passos do desenvolvimento da placa psoriásica, como veremos a seguir.

Imunopatogênese da psoríase: revisando conceitos / Reviewing concepts in the immunopathogenesis of psoriasis

O conhecimento sobre a fisiopatogenia da psoríase possibilitou o desenvolvimento de ferramentas terapêuticas que visam ao bloqueio do seu gatilho imunológico. Paralelamente, citocinas como o TNF têm sido reconhecidas como integrantes da etiopatogenia da psoríase e comorbidades a ela relacionadas. Estudos genéticos e epidemiológicos contribuíram efetivamente para as conclusões a que se tem chegado atualmente sobre esta complexa patologia.

Insights into the pathogenesis of psoriasis led to the development of therapeutic tools aimed at blocking its immunological trigger. In parallel, cytokines such as the tumor necrosis factor (TNF) have been recognized as playing a crucial role in the pathogenesis of psoriasis and its associated comorbidities. Genetic and immunological studies have contributed effectively towards establishing the currently held concepts regarding this complex disease.

Imunopatogênese da psoríase / Immunopathogenesis of psoriasis

A psoríase é doença inflamatória comum, afetando cerca de 1 por cento da população brasileira. Os linfócito T auxiliares (Th17 e Th1) estão envolvidos na imunopatogênese da psoríase. Neste artigo é discutida a interação entre a imunidade inata (especialmente células dendríticas e queratinócitos) e adquirida (linfócitos T) na patogênese da psoríase.

Psoriasis is a common inflammatory disease affecting 1 percent of the Brazilian population. Th17 and Th1cells are involved with the immunopathogenisis of psoriasis. In this article it is discussed the interaction between the innate immunity (especially dendritic cells and keratinocytes) and adaptive immunity (T lymphocytes) in the pathogenesis of psoriasis.

Patogenia de la Psoriasis / Pathogenesis of psoriasis

La psoriasis es una enfermedad inflamatoria crónica caracterizada por hiperplasia de la epidermis debida a hiperproliferación aberrante de los queratinocitos, es genéticamente determinada, inmunomediada por los linfocitos T, y exclusiva del género humano. El propósito de este reporte es la revisión de la patogenia de esta enfermedad y sus avances al momento actual.

Psoriasis is a chronic inflamatory skin disease characterized by excessive growth and aberrant differentiation of keratinocytes, genetically determined and immunomediated. The purpose of this report is to review the pathogenesis of psoriasis at present.

IL-10 Implications in Psoriasis

Interleukin [IL]-10 is a pluripotent cytokine with effects on numerous cell populations, in particular circulating and resident immune cells as well as epithelial cells. With its potent immunoregulatory capacities, its main biological function seems to be the limitation and termination of inflammatory responses. Hence, its low level expression found in psoriasis may have pathophysiological relevance to this immune disease. Remarkably, the induction of IL-10 expression was found by conventional antipsoriatic therapies, supporting the hypothesis that it may be a key cytokine in psoriasis. Furthermore, the first use in clinical trials in patients with established psoriasis showed that it had moderate antipsoriatic effects and was well tolerated. Moreover, long-term application in psoriatic patients in remission showed that it decreases the incidence of relapse and prolongs the disease free interval. The IL-10 antipsoriatic activity is suggested to be due to the effects on different cell populations, including antigen presenting cells and T-cells [type 1/type 2 balance shift], but not through direct effects on keratinocytes. In conclusion, IL-10 seems to have major clinical and therapeutic implications in psoriasis. Further multicenter, placebo-controlled, double blind trials are required to be an established antipsoriatic therapy. We can come to the conclusion that IL-10 genetic polymorphism and expression is potentially a key immune marker in psoriasis

Estudio de enfermedad celíaca en pacientes con psoriasis / Frequency of celiac disease among patients with psoriasis

Background: A possible relationship has been reported between psoriasis and celiac disease, with common pathogenic mechanisms that may need further investigation. Aim: To investigate the presence of clinical and serological markers for celiac disease in a group of Chilean psoriatic patients. Material and methods: We included 80 psoriatic patients (42 males) aged 16 to 79 years, whose serum was tested for antitransglutaminase antibodies (ATGA) and antiendomysial antibodies (AEMA). Patients with weakly positive AEMA tests were also tested for antigliadin antibodies (AGA). Results: In six patients (7.5 percent), AEMA and AGA were positive and one patient was positive for ATGA. An upper gastrointestinal endoscopy and duodenal biopsy was offered to these six patients and five accepted the procedure. Only one had a pathological diagnosis of celiac disease. Conclusions: Only one of 80 patients with psoriasis had celiac disease (1.2 percent). Other four patients with positive serologic markers had a normal duodenal biopsy. This group of patients may have latent celiac disease and they should be followed up.

Increased endocytic activity in monocyte-derived dendritic cells in patients with psoriasis vulgaris.

BACKGROUND & OBJECTIVE: The understanding of the pathogenesis of psoriasis vulgaris has focused on T cell mediated immune disorder for many years. Recent studies provide evidence that dendritic cells may be of major importance as regulatory cells driving the psoriasis tissue reaction, and they are one of the therapeutic targets. In order to further characterize the role of dendritic cells in psoriasis, this study was designed to assess the differentiation of dendritic cells from monocytes (MoDC), the expression of phagocytosis related receptors by MoDC, their endocytic activity for fluorescent beads and lucifer yellow as well as their superoxide generation in patients with psoriasis. METHODS: Twenty eight patients with psoriasis vulgaris and 12 healthy controls were included in the study. MoDC were obtained by culturing monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 5 days. Cell surface expression of CD1a, CD14, CD40, CD80, CD83, CD86, HLA-DR, mannose receptor (MR) and Fcg receptors by MoDC and their endocytosis of dextran and lucifer yellow were analyzed by flow cytometry. Zymosan ingestion was measured to access the phagocytosis of MoDC. RESULTS: Differentiation of monocytes to dendritic cells was upregulated in patients manifested as significantly increased expression of CD40, CD80, CD86 and HLA-DR compared with that in healthy controls (P<0.01). Expression of MR and Fcg receptor II (CD32) by MoDC was significantly increased in patients with psoriasis as well (P<0.01). Endocytosis of dextran but not lucifer yellow in patients was significantly higher than controls (P<0.01), and significantly enhanced phagocytosis by increasing zymosan ingestion was also observed (P<0.01) in patients. Taken together, endocytic and phagocytic activity of MoDC in psoriasis was increased than normal persons. INTERPRETATION & CONCLUSION: Enhanced activity of dendritic cells binding and capturing foreign antigens for subsequent antigen presentation and the initiation of immune responses in psoriasis may contribute to the pathogenesis of the disease. The upregulated expression of MR and the enhanced endocytic activity of DC might be an explanation for the absence of skin infection observed in psoriasis.

Flow cytometric analysis of peripheral T lymphocyte subpopulations in psoriasis

Psoriasis is a common inflammatory skin disorder, has received attention as a target for new pathogenesis and oriented therapies. Autoimmunity and T lymphocyte subsets are suggested to be involved in the development of psoriasis. The aim of this work is to asses the role of T lymphocyte subsets in the pathogenesis of psoriasis. We investigated the peripheral blood lymphocyte subpopulations obtained from psoriatic patient before and after treatment and from healthy controls, using two colour flow cytometry. We found highly significant suppression of total CD[3+] T Cells and CD[3+] CD[56+] NKT lymphocytes in psoriatic patient as compared to control. Also, we observed significant reduction of T helper cells in patients as compared to control. The highly significant reduction of CD[3+] T cell and CD[3+] CD[56+] NKT lymphocytes proved their actively involvement in the development of psoriasis

Anti-gliadin antibody in psoriasis: a case-control study

Psoriasis is a chronic inflammatory skin disorder with a wide variety of clinical presentations. Presence of anti gliadin antibody [AGA] has been reported in 16% of psoriatic patients. This study was designed to determine the frequency of the presence of AGA in psoriatic patients. After recording the demographic data and the severity of disease according to PASI scoring system, serum of 100 psoriatic patients and 100 healthy controls were studied for the presence of AGA using indirect immunofluorescence method. AGA was present in sera of 4 [3 males and one female] psoriatic patients while all controls were negative. Three patients were from 20 to 40 years of age. All four AGA positive patients sufferred from plaque type psoriasis. The disease severity was mild in one, moderate in two, and severe in one patient. None of them sufferred from gastrointestinal problems. Although AGA may be present in the serum of some psoriatic cases, a significant relation between skin lesion and hypersensivity to gluten has not been determined yet. More studies using more specific and sensitive assessment methods and larger sample sizes are suggested

Immunohistochemical study of transforming growth factor - beta in psoriasis: correlation with disease severity

This study examined the expression of transforming growth factor-beta [TGF-beta] in psoriatic as well as normal skin to elucidate its potential involvement in the pathogenesis of psoriasis and to find out the relation between disease severity and its local expression in the skin. When compared with normal skin, TGF-beta expression was absent or diminished in the epidermis of psoriatic lesions which was more evident in the lower epidermis. Both normal and psoriatic specimens showed minimally detectable TGF-beta in the dermis. A statistically significant correlation was found between TGF-beta expression in the epidermis and disease severity [PASI score]. The result suggested that the lack or diminished TGF-beta-mediated growth inhibition may play an important role in the pathogenesis of psoriasis