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Psoriasis and dendritic cells

Jacqueline E Greb, Ari M Goldminz, James T Elder, Mark G Lebwohl, Dafna D Gladman, Jashin J Wu, Nehal N Mehta, Andrew Y Finlay, Alice B Gottlieb
Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations and substantial negative effects on patient quality of life. Psoriasis has a strong, albeit polygenic, genetic basis. Whereas approximately half of the accountable genetic effect of psoriasis maps to the major histocompatibility complex, >70 other loci have been identified, many of which implicate nuclear factor-κB, interferon signalling and the IL-23-IL-23 receptor axis. Psoriasis pathophysiology is characterized by abnormal keratinocyte proliferation and immune cell infiltration in the dermis and epidermis involving the innate and adaptive immune systems, with important roles for dendritic cells and T cells, among other cells...
November 24, 2016: Nature Reviews. Disease Primers
Kathleen M Bonifacio, Norma Kunjravia, James G Krueger, Judilyn Fuentes-Duculan
A Disintegrin-like and Metalloprotease domain containing Thrombospondin type 1 motif-like 5 (ADAMTSL5) is a melanocyte-derived protein that has recently been implicated as an activating antigen for IL-17-producing T cells in psoriasis. There is a potential disconnect between the basal location of the melanocytes in the epidermis and the fact that T-cell infiltrates are seen mostly scattered in the epidermis with very large infiltrates in the dermis. Thus, we hypothesized that ADAMTSL5 may be expressed in other cells aside from melanocytes in skin...
October 2016: Journal of Pigmentary Disorders
Iain Welsby, Stanislas Goriely
Interleukin (IL)-23 plays a central role in the orchestration of inflammatory responses. Produced by dendritic cells and macrophages, this cytokine promotes the protection of the host against mucosal pathogens through the induction of IL-17 and related cytokines by lymphoid cells. Preclinical disease models and association studies in humans have also clearly demonstrated the implication of IL-23 signalling pathway in inflammatory diseases. Indeed, this cytokine is now considered as a major therapeutic target in immune-based pathologies such as psoriasis, ankylosing spondylitis or Crohn's disease...
2016: Advances in Experimental Medicine and Biology
Susanne Mommert, Lisanne Ratz, Kira Herwig, Maren Rost, Ralf Gutzmer, Thomas Werfel
Environmental triggers and genetic factors are supposed to lead to complex gene expression changes in psoriasis and interact in the manifestation of the disease. The histamine H4 receptor (HRH4) is functionally expressed on Th17 cells and plasmacytoid dendritic cells (pDCs) which play a prominent role in the pathogenesis of psoriasis. On pDCs a higher basal expression level of the HRH4 in psoriasis patients compared to healthy controls has been detected. The functional relationship between predisposing genetic variations in the HRH4 gene and psoriasis is yet not known...
October 7, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Yan Wang, Jingxia Zhao, Tingting Di, Mingxing Wang, Zhitong Ruan, Lu Zhang, Xiangjiang Xie, Yujiao Meng, Yan Lin, Xin Liu, Ning Wang, Ping Li
β,β-dimethylacryloyl alkannin (DMA) is a key component of Lithospermum and possesses good efficacy for treating psoriasis. DMA inhibits activated dendritic cells (DCs), but the mechanism is unknown. Therefore, this study aimed to explore the modulation of the TLR7/8 pathway by DMA in psoriasis-activated DCs. Models of psoriasis-like skin lesions were established using BALB/c mice; 8 mice were treated with DMA (2.5mg/kg). Bone marrow cells were isolated and induced into DCs using R848, a TLR7/8 agonist. Splenic CD11c+ cells were detected by flow cytometry...
September 30, 2016: International Immunopharmacology
Hannah Pischon, Moritz Radbruch, Anja Ostrowski, Pierre Volz, Christian Gerecke, Michael Unbehauen, Stefan Hönzke, Sarah Hedtrich, Joachim W Fluhr, Rainer Haag, Burkhard Kleuser, Ulrike Alexiev, Achim D Gruber, Lars Mundhenk
Inflammatory disorders of the skin pose particular therapeutic challenges due to complex structural and functional alterations of the skin barrier. Penetration of several anti-inflammatory drugs is particularly problematic in psoriasis, a common dermatitis condition with epidermal hyperplasia and hyperkeratosis. Here, we tested in vivo dermal penetration and biological effects of dendritic core-multishell-nanocarriers (CMS) in a murine skin model of psoriasis and compared it to healthy skin. In both groups, CMS exclusively localized to the stratum corneum of the epidermis with only very sporadic uptake by Langerhans cells...
October 1, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Amy S Paller, Yael Renert-Yuval, Maria Suprun, Hitokazu Esaki, Margeaux Oliva, Thy Nhat Huynh, Benjamin Ungar, Norma Kunjravia, Rivka Friedland, Xiangyu Peng, Xiuzhong Zheng, Yeriel D Estrada, James G Krueger, Keith A Choate, Mayte Suárez-Fariñas, Emma Guttman-Yassky
BACKGROUND: The ichthyoses are rare genetic disorders associated with generalized scaling, erythema, and epidermal barrier impairment. Pathogenesis-based therapy is largely lacking, since the underlying molecular basis is poorly understood. OBJECTIVE: To characterize molecularly cutaneous inflammation and its correlation with clinical and barrier characteristics. METHODS: We analyzed biopsies from 21 genotyped ichthyosis patients (congenital ichthyosiform erythroderma (n=6), lamellar ichthyosis (n=7), epidermolytic ichthyosis, (n=5) and Netherton syndrome (n=3)) by immunohistochemistry and RT-PCR and compared them with healthy controls, and atopic dermatitis (AD) and psoriasis patients...
August 20, 2016: Journal of Allergy and Clinical Immunology
Mateusz P Poltorak, Christina E Zielinski
The skin immune system comprises a heterogeneous network of local cellular immune mediators. Their complex interplay establishes an efficient first line barrier defense against pathogens and other environmental assaults. It also assures immune homeostasis and tolerance of the commensal microbiota. In psoriasis, a chronic inflammatory skin disease, this skin immune homeostasis is dysregulated resulting in immune cell infiltration and hyperplasia of epidermal keratinocytes. This article is protected by copyright...
August 19, 2016: Experimental Dermatology
Zaidoon Al-Jaderi, Azzam A Maghazachi
Several drugs have been approved for treatment of multiple sclerosis (MS). Dimethyl fumarate (DMF) is utilized as an oral drug to treat this disease and is proven to be potent with less side effects than several other drugs. On the other hand, monomethyl fumarate (MMF), a related compound, has not been examined in greater details although it has the potential as a therapeutic drug for MS and other diseases. The mechanism of action of DMF or MMF is related to their ability to enhance the antioxidant pathways and to inhibit reactive oxygen species...
2016: Frontiers in Immunology
Timo Buhl, Mohamed M Saleh, Michael P Schön
The astounding capacity of the mammalian immune system to cope with almost any microbial antigen is owed to its virtually unlimited repertoire of T- and B-cell receptors. Since self-antigens (or auto-antigens) are also recognized by some of these receptors, several effective mechanisms have evolved to contain and regulate auto-reactivity, and also to prevent catastrophic auto-inflammatory events. This article is protected by copyright. All rights reserved.
August 4, 2016: Experimental Dermatology
Shi-Wei Huang, Yi-Ju Chen, Sin-Ting Wang, Li-Wei Ho, Jun-Kai Kao, Miwako Narita, Masuhiro Takahashi, Chun-Ying Wu, Hsuan-Yu Cheng, Jeng-Jer Shieh
BACKGROUND: The activation of Toll-like receptor 7 (TLR7) in dendritic cells (DCs) plays a crucial role in the pathogenesis of psoriasis. The macrolide antibiotic azithromycin (AZM) had been demonstrated to inhibit the TLR4 agonist-induced maturation and activation of murine bone marrow-derived DCs (BMDCs). OBJECTIVE: To investigate the effects of AZM on the induction of DC maturation and activation by imiquimod (IMQ), a synthetic TLR7 agonist, as well as its potential as a therapeutic agent for psoriasis...
October 2016: Journal of Dermatological Science
Adrien Mossu, Anna Daoui, Francis Bonnefoy, Lucie Aubergeon, Philippe Saas, Sylvain Perruche
Regulation of the inflammatory response involves the control of dendritic cell survival. To our knowledge, nothing is known about the survival of plasmacytoid dendritic cells (pDC) in such situation. pDC are specialized in type I IFN (IFN-I) secretion to control viral infections, and IFN-I also negatively regulate pDC survival during the course of viral infections. In this study, we asked about pDC behavior in the setting of virus-free inflammation. We report that pDC survival was profoundly reduced during different nonviral inflammatory situations in the mouse, through a mechanism independent of IFN-I and TLR signaling...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Pawel Majewski, Monika Majchrzak-Gorecka, Beata Grygier, Joanna Skrzeczynska-Moncznik, Oktawia Osiecka, Joanna Cichy
Neutrophil extracellular traps (NETs), DNA webs released into the extracellular environment by activated neutrophils, are thought to play a key role in the entrapment and eradication of microbes. However, NETs are highly cytotoxic and a likely source of autoantigens, suggesting that NET release is tightly regulated. NET formation involves the activity of neutrophil elastase (NE), which cleaves histones, leading to chromatin decondensation. We and others have recently demonstrated that inhibitors of NE, such as secretory leukocyte protease inhibitor (SLPI) and SerpinB1, restrict NET production in vitro and in vivo...
2016: Frontiers in Immunology
Ling-Juan Zhang, George L Sen, Nicole L Ward, Andrew Johnston, Kimberly Chun, Yifang Chen, Christopher Adase, James A Sanford, Nina Gao, Melanie Chensee, Emi Sato, Yi Fritz, Jaymie Baliwag, Michael R Williams, Tissa Hata, Richard L Gallo
Type 1 interferons (IFNs) promote inflammation in the skin but the mechanisms responsible for inducing these cytokines are not well understood. We found that IFN-β was abundantly produced by epidermal keratinocytes (KCs) in psoriasis and during wound repair. KC IFN-β production depended on stimulation of mitochondrial antiviral-signaling protein (MAVS) by the antimicrobial peptide LL37 and double stranded-RNA released from necrotic cells. MAVS activated downstream TBK1 (TANK-Binding Kinase 1)-AKT (AKT serine/threonine kinase 1)-IRF3 (interferon regulatory factor 3) signaling cascade leading to IFN-β production and then promoted maturation of dendritic cells...
July 19, 2016: Immunity
Farzaneh Rahmani, Nima Rezaei
INTRODUCTION: Expression of various Toll-like receptors (TLR) in keratinocytes (KCs) has offered new insights into the pathogenesis of psoriasis. When plasmacytoid dendritic cells (pDCs) are scarce in established psoriatic lesions, KCs take the responsibility to secrete IFN type 1 through TLR9 activation. Antagonists of TLR7 and TLR8 and anti-IL-12/IL-23 substances have shown promising results in treating psoriasis. AREAS COVERED: References in this study were extracted from Scopus, PubMed and Embase databases by the search term: ('Toll-Like Receptors' OR 'TLR') AND ('Psoriasis' OR 'Arthritis, Psoriatic' OR 'PsA')...
July 4, 2016: Expert Review of Clinical Immunology
Tao Chen, Li-Xin Fu, Li-Wen Zhang, Bin Yin, Pei-Mei Zhou, Na Cao, Yong-Hong Lu
Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, characterized by hyperproliferation of keratinocytes, dilation and growth of dermal capillary vasculature, and cellular infiltration of T cells, dendritic cells (DCs), and neutrophils. Paeoniflorin (PF), the principal component of total glucosides of paeony (TGP), displays anti-inflammatory and antioxidant properties in several animal models. In this study, we investigated the anti-inflammatory effects and mechanisms of PF in imiquimod (IMQ)-induced psoriasis-like mouse model...
August 2016: Canadian Journal of Physiology and Pharmacology
Takahiro Suzuki, Kazuki Tatsuno, Taisuke Ito, Jun-Ichi Sakabe, Atsuko Funakoshi, Yoshiki Tokura
BACKGROUND: In relation to Th17 cell actions, interferon (IFN)-α production by plasmacytoid dendritic cells (pDCs) are involved in the pathogenesis of psoriasis. Vitamin D3 analogues are widely used in the treatment of psoriasis, however, their actions on pDCs are not well understood. OBJECTIVE: To investigate the effects of Vitamin D3 analogue calcipotriol (CAL) on pDCs, focusing on the cytokine production and chemotactic activity. METHODS: We compared in mice the effects of CAL, cyclosporine A (CyA), and triamcinolone acetonide (TA) on the cytokine production by pDCs (IFN-α), conventional DCs (TNF-α), and γd T cells (IL-17A)...
June 3, 2016: Journal of Dermatological Science
Fenli Shao, Tao Tan, Yang Tan, Yang Sun, Xingxin Wu, Qiang Xu
Psoriasis is a chronic inflammatory skin disease with excessive activation of toll-like receptors (TLRs), which play important roles in developing psoriasis. Targeting TLR signaling remains a challenge for treating psoriasis. Here, we found that andrographolide (Andro), a small-molecule natural product, alleviated imiquimod- but not interleukin 23 (IL-23)-induced psoriasis in mice with reducing expressions of IL-23 and IL-1β in the skin. The improvement in imiquimod-induced psoriasis by Andro was not observed in microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) knockout mice...
September 1, 2016: Biochemical Pharmacology
M Llamas-Velasco, P Bonay, M José Concha-Garzón, L Corvo-Villén, A Vara, D Cibrián-Vera, A Sanguino-Pascual, F Sánchez-Madrid, H de la Fuente, E Daudén
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is an inducible enzyme that suppresses the immune response. The role of IDO as a negative regulator of the inflammatory responses has been documented in several experimental autoimmune diseases. OBJECTIVES: To explore the regulation of IDO by immune cells in Psoriasis and its relation with disease severity. METHODS: The expression and activity of IDO have been assessed by RT-PCR, flow cytometry and HPLC in peripheral blood of patients with moderate to severe plaque-type psoriasis...
June 3, 2016: British Journal of Dermatology
Yoshimi Miki, Yuh Kidoguchi, Mariko Sato, Yoshitaka Taketomi, Choji Taya, Kazuaki Muramatsu, Michael H Gelb, Kei Yamamoto, Makoto Murakami
Phospholipase A2 enzymes have long been implicated in the promotion of inflammation by mobilizing pro-inflammatory lipid mediators, yet recent evidence suggests that they also contribute to anti-inflammatory or pro-resolving programs. Group IID-secreted phospholipase A2 (sPLA2-IID) is abundantly expressed in dendritic cells in lymphoid tissues and resolves the Th1 immune response by controlling the steady-state levels of anti-inflammatory lipids such as docosahexaenoic acid and its metabolites. Here, we show that psoriasis and contact dermatitis were exacerbated in Pla2g2d-null mice, whereas they were ameliorated in Pla2g2d-overexpressing transgenic mice, relative to littermate wild-type mice...
July 22, 2016: Journal of Biological Chemistry
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