The role of the immune system in the pathogenesis of psoriasis

Psoriatic involved skin contains an increased number of activated T cells. The mechanism through which these T cells achieve and maintain their activated state is unknown, and both antigen-dependent and -independent mechanisms may contribute. Recently a novel pathway of antigen-independent T-cell activation has been described. This pathway is identified by a monoclonal antibody that binds to a T-cell membrane surface molecule termed "UM4D4.". This molecule is expressed on a minority (20%) of psoriatic peripheral blood T cells but on a majority (75%) of the T cells in lesional skin. Thus, UM4D4 could play a role in antigen-independent T-cell activation in psoriasis. Indeed the monoclonal antibody anti-UM4D4 consistently induces proliferation of psoriatic UM4D4+ T-cell clones. The activity of antigen-dependent pathways are also enhanced in psoriatic epidermis in as much as involved skin relative to uninvolved skin contains an increased number and function of antigen-presenting cells. Upon activation, the lesional T cells release lymphokines. Central to the immune hypothesis of psoriasis is that some of these T-cell lymphokines act on keratinocytes to induce changes characteristic of psoriasis. Indeed lymphokines from lesional psoriatic T-cell clones directly alter in vitro keratinocyte phenotype through induction of intercellular adhesion molecule-1 (ICAM-1) and HLA-DR cell-surface expression. Furthermore, the lymphokines also enhance keratinocyte growth. These data suggest a critical role for the immune system in the pathogenesis of psoriasis.     

The role of the palatine tonsils in the pathogenesis and treatment of psoriasis

Psoriasis is a common chronic skin disease with strong genetic associations and environmental triggers. Patients with psoriasis develop sore throats much more frequently than nonpsoriatic individuals and it is well documented that streptococcal throat infections can trigger the onset of psoriasis, and such infections cause exacerbation of chronic psoriasis. It is now generally accepted that psoriatic lesions are caused by abnormal reactivity of specific T lymphocytes in the skin. However, it has been shown in recent years that activation of specific immunity is always preceded by activation of nonspecific innate immune mechanisms, and that abnormalities in the innate immune system can cause dysregulation in specific immune responses. Here we explore the possible immune mechanisms that are involved in the link between infection of the tonsils and this inflammatory skin disease. Moreover, we survey the literature and discuss the suitability of tonsillectomy as a treatment for psoriasis.     

Critical role of environmental factors in the pathogenesis of psoriasis

Psoriasis is a common cutaneous disease with multifactorial etiology including genetic and non‐genetic factors, such as drugs, smoking, drinking, diet, infection and mental stress. Now, the role of the interaction between environmental factors and genetics are considered to be a main factor in the pathogenesis of psoriasis. However, it is a challenge to explore the mechanisms how the environmental factors break the body balance to affect the onset and development of psoriasis. In this article, we review the pathogenesis of psoriasis and summarize numerous clinical data to reveal the association between environmental factors and psoriasis. In addition, we focus on the mechanisms of environmental risk factors impact on psoriasis and provide a series of potential treatments against environmental risk factors.     

The pathogenesis of psoriasis

Ildamen has a positive effect on the course of psoriasis in patients with cardiovascular diseases. Its effect in psoriasis appears to be explained by its stimulating action on skin beta-adrenoreceptors. The study carried out by the authors confirms the contribution of beta-adrenoreceptors to the pathogenesis of psoriasis.     

脂肪因子在银屑病发病机制中的研究进展

银屑病是一种慢性炎症性皮肤病,患者多伴有系统性代谢性疾病。脂肪组织作为内分泌器官可分泌多种脂肪因子参与多种代谢性疾病和炎症性疾病的发病。目前的研究证实一些脂肪因子可能参与银屑病的发病过程,并且为将来的诊断治疗提供新的生物学标志。     

维生素D及其衍生物在银屑病发病机制和治疗中的作用

 银屑病是一种常见的免疫介导的慢性炎症性皮肤病，以红斑、丘疹、鳞屑为临床表现。迄今为止，银屑病的发病机制尚未完全明确。研究表明，缺乏维生素D（VD）可加重皮肤的炎症反应和免疫失衡，促进角质形成细胞（KC）的增殖，破坏皮肤屏障功能，从而导致银屑病的发生和发展。VD及VD3衍生物（VDAs）对银屑病有较好的治疗作用。本文概述了VD及其衍生物治疗银屑病的作用机制，评价其治疗价值。     

趋化因子在银屑病发病机制中的研究进展

银屑病是一种常见的慢性炎症增生性皮肤病,其皮损的产生和维持需要多种细胞共同作用,在这个过程中,免疫细胞浸润到皮肤,引起表皮角质形成细胞及血管内皮细胞改变.趋化因子是一类控制细胞定向移动的细胞因子,可分为4个亚族,在炎症和感染皮肤的生理反应中,趋化T细胞及其他细胞迁移及定植到皮肤,在银屑病的发病过程中起到了重要的作用.     

β-防御素在银屑病发病机制中的作用

β-防御素是一组小分子抗菌肽,能够抗多种病原微生物感染,促进炎症反应,并对T细胞等发挥趋化作用.研究发现,银屑病发病可能与β-防御素有关.β-防御素可活化银屑病免疫相关的炎症因子,趋化未成熟的树突细胞和记忆T细胞,并通过促分裂素原活化蛋白激酶作用于角质形成细胞产生炎症因子,将固有性免疫和获得性免疫连接起来.未来应深入探讨β-防御素在银屑病发病中的作用,进一步完善银屑病的免疫学发病机制,寻求治疗新靶点.     

Leukotrienes and monohydroxy fatty acids: controversial role in the pathogenesis of psoriasis

The pros and cons concerning the involvement of arachidonic acid metabolism in the pathogenesis of psoriasis are presented. The isolation of arachidonic acid metabolites from psoriatic lesions, their extraordinary biological activity, and the therapeutic efficiency in psoriasis of inhibitors of arachidonic acid metabolism all argue in favor of leukotrienes and monohydroxy fatty acids playing an important role in the development of psoriasis plaques. On the other hand, the lack of specificity of the biochemical findings, the failure to reproduce psoriatic lesions by arachidonic acid metabolites, and the therapeutic activity of drugs that have no effect on arachidonic acid metabolism show that the role of arachidonic acid metabolism in the pathogenesis of psoriasis is still controversial. The availability of selective inhibitors of arachidonic acid-metabolizing enzymes for clinical testing is a prerequisite before pathophysiological conclusions can be made, as the present status of knowledge makes any conclusions premature.     

Innate immunity in the pathogenesis of psoriasis

Psoriasis is a common, immune-mediated inflammatory skin disorder. T helper(h)1 and Th17 lymphocytes contribute to the pathogenesis of psoriasis through the release of inflammatory cytokines that promote further recruitment of immune cells, keratinocyte proliferation and sustained inflammation. The innate immune system is the first line of defence against infection and plays a crucial role in the initiation of the adaptive immune response. The presence of innate immune cells and their products in psoriatic skin plaques suggests a role for innate immunity in this disease. In addition, the innate immune system can direct the development of pathogenic Th cells in psoriasis. In this article, we will summarise the role of the innate immune system in psoriasis with particular emphasis on the role of cytokines, signalling pathways and cells of the innate immune system.     

Antimicrobial peptides in the pathogenesis of psoriasis

One characteristic abnormality of lesional skin in psoriasis is the excessive production of antimicrobial peptides and proteins (AMPs). AMPs typically are small (12-50 amino acids), have positive charge and amphipathic structure, and are found in all living organisms including mammals, insects, plants and invertebrates. These peptides are best known for their integral role in killing pathogenic microorganisms; however, in vertebrates, they are also capable of modifying host inflammatory responses by a variety of mechanisms. In psoriatic lesions, many AMPs are highly expressed, and especially the associations between psoriasis and cathelicidin, β-defensins or S100 proteins have been well studied. Among them, a cathelicidin peptide, LL-37, has been highlighted as a modulator of psoriasis development in recent years. AMPs had been thought to worsen psoriatic lesions but recent evidence has also suggested the possibility that the induction of AMPs expression might improve aspects of the disease. Further investigations are needed to uncover a previously underappreciated role for AMPs in modulating the immune response in psoriasis, and to improve disease without the risks of systemic immunosuppressive approaches.     

The roles of cells and cytokines in the pathogenesis of psoriasis

Psoriasis is considered an immune chronic disease in which T cells are accepted as important. Nowadays, it is believed that psoriasis is most likely a T helper (Th)1/Th17 induced inflammatory disease. However, some other cells, such as endothelial cells, dendritic cells, monocytic cells, neutrophils, keratinocytes, and several cytokines, appear to have, at different stages of the disease, an important role in its pathogenesis. For instance, the response to psoriasis therapy is dependent not only on the inactivation of Th1 and Th17 immune responses but also on the inactivation of dendritic cell products. Moreover, interleukin (IL)-23 deregulation appears to be an independent factor in the pathogenesis of psoriasis. Indeed, currently, the IL-23/Th17 axis is believed to be crucial in psoriasis pathogenesis, and its inhibition appears to be important for therapeutic achievement. This review presents the roles and interactions of cells and cytokines that are related to psoriasis pathogenesis.     

The role of neuropeptides in psoriasis

The pathogenesis of psoriasis is incompletely understood but cutaneous neurogenic inflammation is probably involved. This involvement is suggested by a number of clinical and histological observations. Reports about the distribution of cutaneous nerves and the quantification of nerve growth factor and neuropeptides, including calcitonin gene-related peptide and vasoactive intestinal peptide, in lesional and nonlesional psoriatic skin suggest that sensory neuropeptides contribute to the development of psoriasis. This review summarizes what is known about the role of neurogenic markers in psoriasis.     

Latest aspects in psoriasis pathogenesis

During recent years the understanding of psoriasis pathogenesis has changed essentially. Psoriasis is now considered as a T cell mediated inflammation of the skin. Genetic predisposition and microbial environment cooperate in the induction of an antigen-specific T cell mediated immune response which may persist lifelong. The phenotype of the psoriatic inflammation is determined by the particular functional differentiation of the pathogenic T cells. The progress in understanding the pathogenesis of psoriasis has identified T cells and T cell-derived cytokines as targets for causal treatment approaches that in the near future will change psoriasis therapy considerably.