scholarly journals Psoriasis: Pathogenesis, Comorbidities, and Therapy Updated

2021 ◽  
Vol 22 (6) ◽  
pp. 2979
Author(s):  
Naoko Kanda
Keyword(s):  
Metabolic Diseases ◽  
Retinoic Acid Receptor ◽  
Skin Inflammation ◽  
Dermal Fibroblasts ◽  
Epidermal Keratinocytes ◽  
Orphan Nuclear Receptor ◽  
Special Issue ◽  
Aryl Hydrocarbon ◽  
Aryl Hydrocarbon Receptor Agonist ◽  
Uba Domain

Psoriasis is a chronic inflammatory skin disease characterized by IL-17-dominant abnormal innate and acquired immunity, and the hyperproliferation and aberrant differentiation of epidermal keratinocytes, and comorbid arthritis or cardiometabolic diseases. This Special Issue presented updated information on pathogenesis, comorbidities, and therapy of psoriasis. The pathogenesis of psoriasis may involve the dysfunction of indoleamine 2,3-dioxygenase 2 or of UBA domain containing 1-mediated regulation of CARD14/CARMA2sh. The blood cells of psoriasis patients showed the enhanced oxidative stress/autophagy flux and decreased 20S proteasome activity. Elafin, clusterin, or selenoprotein P may act as biomarkers for psoriasis and comorbid metabolic diseases. The proteomic profile of psoriasis lesions showed the dysfunction of dermal fibroblasts; up-regulation of proinflammatory factors and signal transduction or down-regulation of structural molecules. The skin inflammation in psoriasis may populate certain gut bacteria, such as Staphylococcus aureus and Streptococcus danieliae, which worsen the skin inflammation in turn. The psoriasis-associated pruritus may be caused by immune, nervous, or vascular mechanisms. In addition to current oral treatments and biologics, a new treatment option for psoriasis is now being developed, such as retinoic-acid-receptor-related orphan nuclear receptor γt inhibitors, IL-36 receptor antagonist, or aryl hydrocarbon receptor agonist. Antimicrobial peptides and innate immune cells, involved in the pathogenesis of psoriasis, may be novel therapeutic targets. The pathomechanisms and responses to drugs in collagen diseases are partially shared with and partially different from those in psoriasis. Certain nutrients can exacerbate or regulate the progress of psoriasis. The articles in this Special Issue will encourage attractive approaches to psoriasis by future researchers.

scholarly journals Diversified Stimuli-Induced Inflammatory Pathways Cause Skin Pigmentation

2021 ◽  
Vol 22 (8) ◽  
pp. 3970
Author(s):  
Md Razib Hossain ◽  
Tuba M. Ansary ◽  
Mayumi Komine ◽  
Mamitaro Ohtsuki
Keyword(s):  
Inflammatory Responses ◽  
Light Exposure ◽  
Skin Pigmentation ◽  
Basal Layer ◽  
Decisive Role ◽  
Skin Inflammation ◽  
Dermal Fibroblasts ◽  
Epidermal Keratinocytes ◽  
Hair Color ◽  
Microbial Infection

The production of melanin pigments by melanocytes and their quantity, quality, and distribution play a decisive role in determining human skin, eye, and hair color, and protect the skin from adverse effects of ultraviolet radiation (UVR) and oxidative stress from various environmental pollutants. Melanocytes reside in the basal layer of the interfollicular epidermis and are compensated by melanocyte stem cells in the follicular bulge area. Various stimuli such as eczema, microbial infection, ultraviolet light exposure, mechanical injury, and aging provoke skin inflammation. These acute or chronic inflammatory responses cause inflammatory cytokine production from epidermal keratinocytes as well as dermal fibroblasts and other cells, which in turn stimulate melanocytes, often resulting in skin pigmentation. It is confirmed by some recent studies that several interleukins (ILs) and other inflammatory mediators modulate the proliferation and differentiation of human epidermal melanocytes and also promote or inhibit expression of melanogenesis-related gene expression directly or indirectly, thereby participating in regulation of skin pigmentation. Understanding of mechanisms of skin pigmentation due to inflammation helps to elucidate the relationship between inflammation and skin pigmentation regulation and can guide development of new therapeutic pathways for treating pigmented dermatosis. This review covers the mechanistic aspects of skin pigmentation caused by inflammation.

scholarly journals Unraveling the physiological roles of retinoic acid receptor-related orphan receptor α

2021 ◽  
Author(s):  
Ji Min Lee ◽  
Hyunkyung Kim ◽  
Sung Hee Baek
Keyword(s):  
Retinoic Acid ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Metabolic Diseases ◽  
Retinoic Acid Receptor ◽  
Critical Role ◽  
Orphan Receptor ◽  
Orphan Nuclear Receptor ◽  
Functional Link ◽  
Acid Receptor

AbstractRetinoic acid receptor-related orphan receptor-α (RORα) is a member of the orphan nuclear receptor family and functions as a transcriptional activator in response to circadian changes. Circadian rhythms are complex cellular mechanisms regulating diverse metabolic, inflammatory, and tumorigenic gene expression pathways that govern cyclic cellular physiology. Disruption of circadian regulators, including RORα, plays a critical role in tumorigenesis and facilitates the development of inflammatory hallmarks. Although RORα contributes to overall fitness among anticancer, anti-inflammatory, lipid homeostasis, and circadian clock mechanisms, the molecular mechanisms underlying the mode of transcriptional regulation by RORα remain unclear. Nonetheless, RORα has important implications for pharmacological prevention of cancer, inflammation, and metabolic diseases, and understanding context-dependent RORα regulation will provide an innovative approach for unraveling the functional link between cancer metabolism and rhythm changes.

scholarly journals GLK-IKKβ signaling induces dimerization and translocation of the AhR-RORγt complex in IL-17A induction and autoimmune disease

2018 ◽  
Vol 4 (9) ◽  
pp. eaat5401 ◽  
Author(s):  
Huai-Chia Chuang ◽  
Ching-Yi Tsai ◽  
Chia-Hsin Hsueh ◽  
Tse-Hua Tan
Keyword(s):  
T Cells ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Nuclear Translocation ◽  
Retinoic Acid Receptor ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Orphan Nuclear Receptor ◽  
Tcr Signaling ◽  
Aryl Hydrocarbon

Retinoic-acid-receptor-related orphan nuclear receptor γt (RORγt) controls the transcription of interleukin-17A (IL-17A), which plays critical roles in the pathogenesis of autoimmune diseases. Severity of several human autoimmune diseases is correlated with frequencies of germinal center kinase–like kinase (GLK) (also known as MAP4K3)–overexpressing T cells; however, the mechanism of GLK overexpression–induced autoimmunity remains unclear. We report the signal transduction converging on aryl hydrocarbon receptor (AhR)–RORγt interaction to activate transcription of the IL-17A gene in T cells. T cell–specific GLK transgenic mice spontaneously developed autoimmune diseases with selective induction of IL-17A in T cells. In GLK transgenic T cells, protein kinase Cθ (PKCθ) phosphorylated AhR at Ser36 and induced AhR nuclear translocation. AhR also interacted with RORγt and transported RORγt into the nucleus. IKKβ (inhibitor of nuclear factor κB kinase β)–mediated RORγt Ser489 phosphorylation induced the AhR-RORγt interaction. T cell receptor (TCR) signaling also induced the novel RORγt phosphorylation and subsequent AhR-RORγt interaction. Collectively, TCR signaling or GLK overexpression induces IL-17A transcription through the IKKβ-mediated RORγt phosphorylation and the AhR-RORγt interaction in T cells. Our findings suggest that inhibitors of GLK or the AhR-RORγt complex could be used as IL-17A–blocking agents for IL-17A–mediated autoimmune diseases.

scholarly journals Interleukin-22 and keratinocytes; pathogenic implications in skin inflammation

2021 ◽  
Author(s):  
Masutaka Furue ◽  
Mihoko Furue
Keyword(s):  
Chemical Sensor ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Lymphoid Cells ◽  
Epidermal Keratinocytes ◽  
Keratinocyte Proliferation ◽  
Interleukin 22 ◽  
Aryl Hydrocarbon ◽  
Group 3 ◽  
Related Proteins

Interleukin (IL)-22 is produced from immune cells such as T helper (Th)22 cells, Th17/22 cells, and group 3 innate lymphoid cells. IL-22 signals via the IL-22 receptor 1(IL-22R1) and the IL-10 receptor 2 (IL-10R2). As the IL-22R1/IL-10R2 heterodimer is preferentially expressed on border tissue between the host and the environment, IL-22 is believed to be involved in border defense. Epidermal keratinocytes are the first-line skin barrier and express IL-22R1/IL-10R2. IL-22 increases keratinocyte proliferation but inhibits differentiation. Aryl hydrocarbon receptor (AHR) is a chemical sensor and an essential transcription factor for IL-22 production. In addition, AHR also upregulates the production of barrier-related proteins such as filaggrin in keratinocytes, suggesting a pivotal role for the AHR-IL-22 axis in regulating the physiological skin barrier. Although IL-22 signatures are elevated in atopic dermatitis and psoriasis, their pathogenic and/or protective implications are not fully understood.

scholarly journals The Orphan Nuclear Receptor 4A1: A Potential New Therapeutic Target for Metabolic Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Lei Zhang ◽  
Qun Wang ◽  
Wen Liu ◽  
Fangyan Liu ◽  
Ailing Ji ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Nuclear Receptor ◽  
Metabolic Diseases ◽  
Early Response ◽  
Orphan Receptor ◽  
Special Focus ◽  
Orphan Nuclear Receptor ◽  
Physiological Functions ◽  
The Impact

Orphan nuclear receptor 4A1 (NR4A1) is a transcriptional factor of the nuclear orphan receptor (NR4A) superfamily that has sparked interest across different research fields in recent years. Several studies have demonstrated that ligand-independent NR4A1 is an immediate-early response gene and the protein product is rapidly induced by a variety of stimuli. Hyperfunction or dysfunction of NR4A1 is implicated in various metabolic processes, including carbohydrate metabolism, lipid metabolism, and energy balance, in major metabolic tissues, such as liver, skeletal muscle, pancreatic tissues, and adipose tissues. No endogenous ligands for NR4A1 have been identified, but numerous compounds that bind and activate or inactivate nuclear NR4A1 or induce cytoplasmic localization of NR4A1 have been identified. This review summarizes recent advances in our understanding of the molecular biology and physiological functions of NR4A1. And we focus on the physiological functions of NR4A1 receptor to the development of the metabolic diseases, with a special focus on the impact on carbohydrate and lipid metabolism in skeletal muscle, liver, adipose tissue, and islet.

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