The role of GNLY gene polymorphisms in psoriasis pathogenesis

Ermis, Esra; Çelik, Sevim; Solak, Nilgün; Genç, Güneş Çakmak; Dursun, Ahmet

doi:10.1590/abd1806-4841.20198188

Cited by 13 publications

(11 citation statements)

References 25 publications

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“…Granulysin is a cytolytic antimicrobial peptide, and secreted with perforin and granzyme by NK and CD8 + T cells. The studies indicated increased granulysin positive cells in lesions and peripheral blood of patients and there is a link between granulysin and severe patients ( 315 , 322 ). Ermis et al.…”

Section: Natural Killer Maturation Phenotypes Distribution and Funcmentioning

confidence: 99%

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The Role of Natural Killer Cells in Autoimmune Diseases

et al. 2021

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Natural killer (NK) cells, the large granular lymphocytes differentiated from the common lymphoid progenitors, were discovered in early 1970’s. They are members of innate immunity and were initially defined by their strong cytotoxicity against virus-infected cells and by their important effector functions in anti-tumoral immune responses. Nowadays, NK cells are classified among the recently discovered innate lymphoid cell subsets and have capacity to influence both innate and adaptive immune responses. Therefore, they can be considered as innate immune cells that stands between the innate and adaptive arms of immunity. NK cells don’t express T or B cell receptors and are recognized by absence of CD3. There are two major subgroups of NK cells according to their differential expression of CD16 and CD56. While CD16+CD56dim subset is best-known by their cytotoxic functions, CD16-CD56bright NK cell subset produces a bunch of cytokines comparable to CD4+ T helper cell subsets. Another subset of NK cells with production of interleukin (IL)-10 was named as NK regulatory cells, which has suppressive properties and could take part in immune-regulatory responses. Activation of NK cells is determined by a delicate balance of cell-surface receptors that have either activating or inhibitory properties. On the other hand, a variety of cytokines including IL-2, IL-12, IL-15, and IL-18 influence NK cell activity. NK-derived cytokines and their cytotoxic functions through induction of apoptosis take part in regulation of the immune responses and could contribute to the pathogenesis of many immune mediated diseases including ankylosing spondylitis, Behçet’s disease, multiple sclerosis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus and type-1 diabetes. Dysregulation of NK cells in autoimmune disorders may occur through multiple mechanisms. Thanks to the rapid developments in biotechnology, progressive research in immunology enables better characterization of cells and their delicate roles in the complex network of immunity. As NK cells stand in between innate and adaptive arms of immunity and “bridge” them, their contribution in inflammation and immune regulation deserves intense investigations. Better understanding of NK-cell biology and their contribution in both exacerbation and regulation of inflammatory disorders is a requisite for possible utilization of these multi-faceted cells in novel therapeutic interventions.

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Section: Natural Killer Maturation Phenotypes Distribution and Funcmentioning

confidence: 99%

“…Ermis et al. showed that Granulysin rs7908 CC genotype and C allele had a protective effect against psoriasis and decreased the disease severity ( 322 ).…”

Section: Natural Killer Maturation Phenotypes Distribution and Funcmentioning

confidence: 99%

The Role of Natural Killer Cells in Autoimmune Diseases

et al. 2021

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“…An abundance of T H 17-linked transcripts was immediately apparent. In addition to the known PV markers IL17F and CXCL13 (9), these PV-specific up-regulated DEGs include granulysin GNLY and CTLA4, whose loci have been linked genetically to PV (41,42), KLRB1, which is down-regulated by the tumor necrosis factor- blocker alefacept in psoriatic lesions (43), MGAT4, which is downregulated during ustekinumab treatment of psoriatic arthritis (44), and PIK3R1 whose germline loss of function impairs cutaneous immunity (45). We also detected recurrent overexpression of signaling components such as MAP3K4 and PTPN13 restricted to the Trm1 and Trm3 classes, possibly helping explain why such…”

Section: Distinct Cell Type-specific Patterning Differentiates Forms ...mentioning

confidence: 99%

Classification of human chronic inflammatory skin disease based on single-cell immune profiling

et al. 2022

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Inflammatory conditions represent the largest class of chronic skin disease, but the molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting the complex mixture of immune and stromal cell perturbations in inflammatory skin disease states. We single-cell–profiled CD45 + immune cell transcriptomes from skin samples of 31 patients (7 atopic dermatitis, 8 psoriasis vulgaris, 2 lichen planus (LP), 1 bullous pemphigoid (BP), 6 clinical/histopathologically indeterminate rashes, and 7 healthy controls). Our data revealed active proliferative expansion of the T reg and Trm components and universal T cell exhaustion in human rashes, with a relative attenuation of antigen-presenting cells. Skin-resident memory T cells showed the greatest transcriptional dysregulation in both atopic dermatitis and psoriasis, whereas atopic dermatitis also demonstrated recurrent abnormalities in ILC and CD8 + cytotoxic lymphocytes. Transcript signatures differentiating these rash types included genes previously implicated in T helper cell (T H 2)/T H 17 diatheses, segregated in unbiased functional networks, and accurately identified disease class in untrained validation data sets. These gene signatures were able to classify clinicopathologically ambiguous rashes with diagnoses consistent with therapeutic response. Thus, we have defined major classes of human inflammatory skin disease at the molecular level and described a quantitative method to classify indeterminate instances of pathologic inflammation. To make this approach accessible to the scientific community, we created a proof-of-principle web interface (RashX), where scientists and clinicians can visualize their patient-level rash scRNA-seq–derived data in the context of our T H 2/T H 17 transcriptional framework.

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“…Similarly, the frequency of psoriatic lesion GNLY + NK cells is increased relative to healthy controls and healthy non-psoriatic skin [102]. Interestingly, genetic analyses suggest a relationship between GNLY polymorphisms and psoriasis [103]. On the other hand, a seemingly contrasting report suggested that the expression of Fas ligand in NK cells isolated from the peripheral blood does not differ between psoriasis patients and healthy control subjects [101].…”

Section: Cytotoxic Function Of Nk Cells In Psoriasismentioning

confidence: 99%

Role of Innate Immune Cells in Psoriasis

Sato

Ogawa

Okuyama

2020

IJMS

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Psoriasis is a chronic inflammatory skin condition caused by a combination of hereditary and environmental factors. Its development is closely related to the adaptive immune response. T helper 17 cells are major IL-17-producing cells, a function that plays an important role in the pathogenesis of psoriasis. However, recent findings have demonstrated that innate immune cells also contribute to the development of psoriasis. Innate lymphoid cells, γδ T cells, natural killer T cells, and natural killer cells are activated in psoriasis, contributing to disease pathology through IL-17-dependent and -independent mechanisms. The present review provides an overview of recent findings, demonstrating a role for innate immunity in psoriasis.

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The role of GNLY gene polymorphisms in psoriasis pathogenesis

Cited by 13 publications

References 25 publications

The Role of Natural Killer Cells in Autoimmune Diseases

The Role of Natural Killer Cells in Autoimmune Diseases

Classification of human chronic inflammatory skin disease based on single-cell immune profiling

Role of Innate Immune Cells in Psoriasis

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