Current Concepts of Psoriasis Immunopathogenesis Vičić, Marijana; Kaštelan, Marija; Brajac, Ines ...
International journal of molecular sciences,
10/2021, Letnik:
22, Številka:
21
Journal Article
Recenzirano
Odprti dostop
Psoriasis is a recurrent, chronic, immune-mediated, systemic inflammatory disease of the skin, joints, and other organic systems. After atopic dermatitis, chronic stationary psoriasis is the most ...common inflammatory skin disease, affecting an average of 2-4% of the world's population. The disease carries a significant burden due to its numerous comorbidities and the major impact on patients' social and emotional aspects of life. According to current knowledge, psoriasis is a multifactorial disease that occurs in genetically predisposed individuals under various environmental factors, which trigger an immune response disorder with a series of complex inflammatory cascades. The disease is initiated and maintained by mutual interaction of the innate and adaptive immune cells, primarily dendritic cells, T lymphocytes, and keratinocytes, whose leading role alternates at different stages of the disease, consisting mainly in the IL-23/Th17 pathway. Inflammatory events result in consequent epidermal and dermal changes and evolution of the characteristic psoriatic phenotype, respectively. This paper aims to present a comprehensive overview of current knowledge on psoriasis genetic and environmental etiological factors, immunopathogenesis, and the leading cellular and cytokine participants in the inflammatory pathways of this disease.
Lichen planus is a chronic disease affecting the skin, appendages, and mucous membranes. A cutaneous lichen planus is a rare disease occurring in less than 1% of the general population, while oral ...illness is up to five times more prevalent; still, both forms equally impair the patient's quality of life. The etiology of lichen planus is not entirely understood. Yet, immune-mediated mechanisms have been recognized since environmental factors such as hepatitis virus infection, mechanical trauma, psychological stress, or microbiome changes can trigger the disease in genetically susceptible individuals. According to current understanding, lichen planus immunopathogenesis is caused by cell-mediated cytotoxicity, particularly cytotoxic T lymphocytes, whose activity is further influenced by Th1 and IL-23/Th-17 axis. However, other immunocytes and inflammatory pathways complement these mechanisms. This paper presents a comprehensive insight into the actual knowledge about lichen planus, with the causal genetic and environmental factors being discussed, the immunopathogenesis described, and the principal effectors of its inflammatory circuits identified.
Abstract Vitiligo and halo nevus are immune-mediated skin diseases that have a similar pathogenesis and involve cellular cytotoxicity mechanisms that are not yet fully understood. In this study, we ...investigated the expression patterns of the cytolytic molecule granulysin (GNLY) in different cytotoxic cells in skin samples of vitiligo and halo nevus. Skin biopsies were taken from perilesional and lesional skin of ten vitiligo patients, eight patients with halo nevus and ten healthy controls. We analysed the expression of GNLY by immunohistochemistry in CD8+ and CD56+ NK cells. A significantly higher accumulation of GNLY+, CD8+ GNLY+ and fewer CD56+ GNLY+ cells was found in the lesional skin of vitiligo and halo nevus than in the healthy skin. These cells were localised in the basal epidermis and papillary dermis, suggesting that GNLY may be involved in the immune response against melanocytes. Similarly, but to a lesser extent, upregulation of GNLY+ and CD8+ GNLY+ cells was observed in the perilesional skin of vitiligo and halo nevus compared to healthy controls. In this study, we demonstrated for the first time an increased expression of CD8+ GNLY+ T lymphocytes and CD56+ GNLY+ NK cells in lesions of vitiligo and halo nevus, indicating the role of GNLY in the pathogenesis of both diseases.
Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss. Despite the growing knowledge ...about AA, its exact cause still needs to be understood. However, immunity and genetic factors are affirmed to be critical in AA development. While the genome-wide association studies proved the innate and acquired immunity involvement, AA mouse models implicated the IFN-γ- and cytotoxic CD8+ T-cell-mediated immune response as the main drivers of disease pathogenesis. The AA hair loss is caused by T-cell-mediated inflammation in the HF area, disturbing its function and disrupting the hair growth cycle without destroying the follicle. Thus, the loss of HF immune privilege, autoimmune HF destruction mediated by cytotoxic mechanisms, and the upregulation of inflammatory pathways play a crucial role. AA is associated with concurrent systemic and autoimmune disorders such as atopic dermatitis, vitiligo, psoriasis, and thyroiditis. Likewise, the patient’s quality of life (QoL) is significantly impaired by morphologic disfigurement caused by the illness. The patients experience a negative impact on psychological well-being and self-esteem and may be more likely to suffer from psychiatric comorbidities. This manuscript aims to present the latest knowledge on the pathogenesis of AA, which involves genetic, epigenetic, immunological, and environmental factors, with a particular emphasis on immunopathogenesis.
Authentic leadership is a positive leadership theory, conceptualized under the influence of positive psychology and positive organizational behaviour movement. Although it has become a recognized ...leadership theory, it is still somewhat neglected in the hospitality literature. To address this gap, the paper seeks to develop and test a conceptual model linking authentic leadership to organizational performance in the hospitality context. Hypotheses were tested using hierarchical multiple regression analysis on a sample of 226 employees from 24 hotels in Croatia. The research results confirmed the positive impact of authentic leadership on hotels’ operational performance, which was mediated by followers’ job satisfaction and performance. There was no empirical support for the hypothesized impact of authentic leadership on hotels’ financial performance. The findings suggest that authentic leadership behaviours, together with positive organisational settings, characterized by flexible organizational structure, are more likely to enhance desirable employees’ attitudes and behaviours, resulting in improved organizational performance.
Psoriasis is considered to be a cytokine-driven immune-mediated disease, although the cell cytotoxicity mechanisms involved remain unrecognized. Herein, we analyzed granulysin expression in different ...lymphocyte subsets of peripheral blood of 40 psoriatic patients (20 with severe and 20 with mild psoriasis) and seven sample of psoriatic skin. The simultaneous detection of intracellular granulysin and cell surface antigens was performed using flow cytometry in peripheral blood and immunohistochemistry in skin lesions. The frequency of granulysin+ cells, mean fluorescence intensity for granulysin, and the frequency of CD8+ T lymphocytes, NK cells, and NKT cells expressing granulysin molecules in peripheral blood were significantly higher in patients with severe psoriasis compared to mild disease and healthy individuals. These were also correlated with disease severity. Furthermore, granulysin+ cells, CD8+granulysin+ T lymphocytes, and CD56+granulysin+ NK cells were present in a higher frequency in the epidermal basal cell layer and in the dermal infiltrate of lesional skin as compared to non-lesional and healthy skin. In conclusion, granulysin+ cytotoxic cells are upregulated in blood and lesions of patients with psoriasis suggesting the involvement of granulysin mediated cytotoxicity in psoriasis pathogenesis.
Vitiligo is an acquired immune-mediated disorder of pigmentation clinically characterized by well-defined depigmented or chalk-white macules and patches on the skin. The prevalence of vitiligo varies ...by geographical area, affecting 0.5% to 2% of the population. The disease imposes a significant psychological burden due to its major impact on patients’ social and emotional aspects of life. Given its autoimmune background, vitiligo is frequently associated with other autoimmune diseases or immune-mediated diseases. Vitiligo is a multifaceted disorder that involves both genetic predisposition and environmental triggers. In recent years, major predisposing genetic loci for the development of vitiligo have been discovered. The current findings emphasize the critical role of immune cells and their mediators in the immunopathogenesis of vitiligo. Oxidative-stress-mediated activation of innate immunity cells such as dendritic cells, natural killer, and ILC-1 cells is thought to be a key event in the early onset of vitiligo. Innate immunity cells serve as a bridge to adaptive immunity cells including T helper 1 cells, cytotoxic T cells and resident memory T cells. IFN-γ is the primary cytokine mediator that activates the JAK/STAT pathway, causing keratinocytes to produce the key chemokines CXCL9 and CXCL10. Complex interactions between immune and non-immune cells finally result in apoptosis of melanocytes. This paper summarizes current knowledge on the etiological and genetic factors that contribute to vitiligo, with a focus on immunopathogenesis and the key cellular and cytokine players in the disease’s inflammatory pathways.
Lichen planus is a chronic mucocutanous disorder histopathologically characterized with a keratinocytes apoptosis, subsequent basal cell layer liquefaction and accumulation of the inflammatory ...infiltrate in papillary dermis. A formation of apoptotic bodies in basal cell layer is due to a cytotoxic lymphocyte attack to the basal keratinocytes. It has been demonstrated that the cytotoxic molecules included in this attack are perforin and granzyme B. Both molecules are found upregulated in CD8+ lymphocytes that are in close contact to keratinocytes. However, their amount is lower in lichen planus than in other skin disease characterized by liquefaction and vacuolar degeneration of the basal epidermal layer. This could speculate about other cytotoxic molecule such as granulysin that could mediate keratinocyte apoptosis. Therefore, in this article we hypothesize about the crucial role of granulysin molecule in keratinocytes killing that could contribute to a lichen planus pathogenesis.
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