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IL-17 and psoriasis

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https://www.readbyqxmd.com/read/28319618/new-biologics-in-psoriasis-an-update-on-il-23-and-il-17-inhibitors
#1
Joanna Dong, Gary Goldenberg
As immune-related pathways involved in the pathogenesis of psoriasis are elucidated, new biologic treatments targeting these steps of the psoriatic immune cascade are developed. In this article, we review the literature on IL-23 and IL-17 inhibitors in the pipeline for use in moderate to severe psoriasis. Numerous pipeline biologic therapies, including risankizumab, guselkumab, tildrakizumab, ixekizumab, and brodalumab, are being investigated in phase 2 and 3 studies to establish the efficacy and safety of these new agents...
February 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28303135/a-human-lin-cd123-cd127-low-population-endowed-with-ilc-features-and-migratory-capabilities-contributes-to-immunopathological-hallmarks-of-psoriasis
#2
Luz María Mora-Velandia, Octavio Castro-Escamilla, Andrés González Méndez, Cristina Aguilar-Flores, Martha Velázquez-Avila, María Isabel Tussié-Luna, Juan Téllez-Sosa, César Maldonado-García, Fermín Jurado-Santacruz, Eduardo Ferat-Osorio, Jesus Martínez-Barnetche, Rosana Pelayo, Laura C Bonifaz
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127(-) ILC populations and an early ILC precursor (EILP) CD127(low). ILC development has predominately been investigated in mouse models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28301691/interleukin-32-is-highly-expressed-in-lesions-of-hidradenitis-suppurativa
#3
R Thomi, D Yerly, N Yawalkar, D Simon, C Schlapbach, R E Hunger
BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Its immunopathogenic mechanisms are still poorly understood. Previous studies could demonstrate that the pro-inflammatory cytokine Interleukin-32 (IL-32) is implicated in the pathogenesis of other inflammatory diseases. OBJECTIVES: The aim of our study was to investigate the tissue expression and systemic levels of IL-32 as well as its cellular sources in HS patients in comparison to healthy donors and to patients suffering from two other inflammatory skin diseases: psoriasis (PS) and atopic dermatitis (AD)...
March 16, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28299442/interleukin-il-18-cooperatively-with-il-23-induces-prominent-inflammation-and-enhances-psoriasis-like-epidermal-hyperplasia
#4
Noriko Shimoura, Hiroshi Nagai, Susumu Fujiwara, Haruki Jimbo, Takayuki Yoshimoto, Chikako Nishigori
The interleukin (IL)-23/IL-17 axis is strongly implicated in the pathogenesis of psoriasis. Previous studies showed that IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index. However, the mechanism whereby IL-18 affects disease severity remains unknown. In this study, we investigated the effects of IL-18 on a psoriasis-like skin inflammation model induced by recombinant mouse IL-23. We found that IL-18, cooperatively with IL-23, induced prominent inflammation and enhanced psoriasis-like epidermal hyperplasia...
March 15, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28296664/histomorphology-and-immunophenotype-of-eczematous-skin-lesions-revisited-skin-biopsies-are-not-reliable-in-differentiating-allergic-contact-dermatitis-irritant-contact-dermatitis-and-atopic-dermatitis
#5
Verena G Frings, Almut Böer-Auer, Kristine Breuer
Lesions of allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), and atopic dermatitis (AD) share similar clinical features and thus, their diagnosis can be challenging. The aim of this study was to reassess histopathology and immunophenotyping properties to distinguish between ACD, ICD, and AD. Charts of patients with eczema, who had undergone complete routine diagnostic workup (skin biopsies, patch tests, skin prick tests, and respectively or serum IgE levels), were reviewed. Thirty-five skin biopsy specimens of 28 patients (mean age 64 ± 15 years; ♀ = 13 ♂ = 15) with clear diagnosis of ACD (n = 15), ICD (n = 6), or AD (n = 14) were analyzed...
March 10, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28285360/kynurenic-acid-downregulates-il-17-1l-23-axis-in-vitro
#6
Sanam Salimi Elizei, Malihe-Sadat Poormasjedi-Meibod, Xia Wang, Maryam Kheirandish, Aziz Ghahary
Exploring the function of interleukin (IL) 17 and related cytokine interactions have been proven useful toward understanding the role of inflammation in autoimmune diseases. Production of the inflammatory cytokine IL-23 by dendritic cells (DC's) has been shown to promote IL-17 expression by Th17 cells. It is well established that Th17 cells play an important role in several autoimmune diseases including psoriasis and alopecia. Our recent investigations have suggested that Kynurenine-rich environment can shift a pro-inflammatory response to an anti-inflammatory response, as is the case in the presence of the enzyme Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan degradation and Kynurenine (Kyn) production...
March 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28280792/inhibition-of-interleukin-17-a-but-not-interleukin-17f-signaling-lowers-blood-pressure-and-reduces-end-organ-inflammation-in-angiotensin-ii-induced-hypertension
#7
Mohamed A Saleh, Allison E Norlander, Meena S Madhur
OBJECTIVES: To characterize the T cell subsets producing interleukin 17 (IL-17) isoforms A and F in hypertensive kidneys and vessels and determine whether inhibition of IL-17 signaling lowers blood pressure and end-organ damage in a mouse model of hypertension. BACKGROUND: T cell derived cytokines play a central role in the pathophysiology of hypertension and contribute to end-organ dysfunction. We previously showed that mice genetically deficient in IL-17A exhibited blunted hypertension and reduced renal and vascular dysfunction in response to angiotensin II (Ang II) infusion...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28274739/dual-role-of-act1-in-keratinocyte-differentiation-and-host-defense-traf3ip2-silencing-alters-keratinocyte-differentiation-while-inhibiting-il-17-responses
#8
Sylviane Lambert, William R Swindell, Lam C Tsoi, Stefan W Stoll, James T Elder
TRAF3IP2 is a candidate psoriasis susceptibility gene encoding Act1, an adaptor protein with ubiquitin ligase activity that couples the IL-17 receptor to downstream signaling pathways. We investigated the role of Act1 in keratinocyte responses to IL-17 using a tetracycline inducible shRNA targeting TRAF3IP2. Tet exposure for seven days effectively silenced TRAF3IP2 mRNA and Act1 protein, resulting in 761 genes with significant changes in expression (495 down, 266 up, >1.5-fold, p<0.05). Gene Ontology analysis revealed that genes affected by TRAF3IP2 silencing are involved in epidermal differentiation, with early differentiation genes (KRT1, KRT10, DSC1, DSG1) being downregulated and late differentiation genes (SPRR2, SPRR3, LCE3) being upregulated...
March 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28270233/mechanistic-rationales-for-targeting-interleukin-17a-in-spondyloarthritis
#9
REVIEW
Siba P Raychaudhuri, Smriti K Raychaudhuri
The term spondyloarthritis (SpA) is used to describe a group of inflammatory autoimmune diseases, including ankylosing spondylitis and psoriatic arthritis, with common genetic risk factors and clinical features. SpA is clinically distinct from rheumatoid arthritis and typically affects the spine, sacroiliac joints, entheses, and, less commonly, peripheral joints. Although the pathogenesis of SpA is not fully understood, recent findings have identified the interleukin (IL)-17 pathway as a key mediator of disease pathogenesis...
March 8, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28243466/update-on-interleukin-17-a-role-in-the-pathogenesis-of-inflammatory-arthritis-and-implication-for-clinical-practice
#10
REVIEW
Pierre Miossec
Interleukin-17 (IL-17A) is a cytokine critical for the acute defence against extracellular bacterial and fungal infections. Excess production during chronic inflammation has been associated with many inflammatory and autoimmune disorders. The present review describes the key molecules of the IL-17 pathway, which are or could be targeted for treatment. Since targeting of IL-17A may affect defence mechanisms, the pathogenesis of such possible adverse events is analysed. Then the contributions of IL-17 to bone changes in various forms of arthritis are discussed...
2017: RMD Open
https://www.readbyqxmd.com/read/28239238/cytokine-imbalance-as-a-common-mechanism-in-both-psoriasis-and-rheumatoid-arthritis
#11
Yong Tan, Qiu Qi, Cheng Lu, Xuyan Niu, Yanping Bai, Chunyan Jiang, Yang Wang, Youwen Zhou, Aiping Lu, Cheng Xiao
Psoriasis (PS) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases. Previous studies showed that these two diseases had a common pathogenesis, but the precise molecular mechanism remains unclear. In this study, RNA sequencing of peripheral blood mononuclear cells was employed to explore both the differentially expressed genes (DEGs) of 10 PS and 10 RA patients compared with those of 10 healthy volunteers and the shared DEGs between these two diseases. Bioinformatics network analysis was used to reveal the connections among the shared DEGs and the corresponding molecular mechanism...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28239073/effects-of-topical-application-of-betamethasone-on-imiquimod-induced-psoriasis-like-skin-inflammation-in-mice
#12
Hiroki Mori, Kojo Arita, Takayuki Yamaguchi, Midori Hirai, Yoichi Kurebayashi
Psoriasis is a chronic inflammatory skin disease mediated by dysregulated auto-reactive immune system. In this study, in order to confirm and further extend the pharmacological basis of topical steroids in psoriasis therapy, we investigated the effect of betamethasone ointment on imiquimod (IMQ)-induced skin inflammation in mice. In BALB/c mice, topical IMQ at the dose of 250 µg each on both sides of the ear induced marked psoriasis-like skin inflammation within 5 days. The same dose of IMQ produced only slight to moderate skin inflammation even on Day 7 in CB-17 scid mice...
September 9, 2016: Kobe Journal of Medical Sciences
https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#13
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28165883/the-role-of-il-23-in-the-treatment-of-psoriasis
#14
Lluís Puig
The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. Human IL-23 is primarily produced by antigen-presenting cells and induces and maintains differentiation of Th17 cells and Th22 cells, a primary cellular source of proinflammatory cytokines such as IL-17 and IL-22, which mediate the epidermal hyperplasia, keratinocyte immune activation and tissue inflammation inherent in psoriasis. Agents that target the p40 subunit common to both IL-12 and IL-23 have shown robust clinical activity, but selectivity for IL-23p19 could offer advantages in efficacy and safety with respect to anti-p40 blockade...
February 6, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28129604/formula-psori-cm01-inhibits-the-inflammatory-cytokine-and-chemokine-release-in-keratinocytes-via-nf-%C3%AE%C2%BAb-expression
#15
Ling Han, Jing Sun, Chuan-Jian Lu, Rui-Zhi Zhao, Yue Lu, Han-Jie Lin, Jian-An Wei
Psoriasis is a common chronic inflammatory disease in which T-helper 1(Th1) and T-helper 17(Th17) cells play an important role in its pathology. Formula PSORI-CM01 was a novel formulated Chinese medicine used for psoriasis therapy. It had been demonstrated previously that PSORI-CM01 and serum contained Formula PSORI-CM01 (PCM01CS) could improve psoriasis by inhibiting the epithelial hyperplasia, how PSORI-CM01 affects inflammatory cytokine and chemokine in dermis is still unknown. In this study we found PSORI-CM01 pre-treated 3days before IMQ painting could ameliorated IMQ-induced mice skin lesion as PASI score was apparently reduced...
January 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28124315/relevance-of-in-vitro-3-d-skin-models-in-dissecting-cytokine-contribution-to-psoriasis-pathogenesis
#16
REVIEW
A Chiricozzi, M Romanelli, S Panduri, E Donetti, F Prignano
Psoriasis is a chronic skin disease characterized by the activation of various T cell subsets secreting IFNγ, IL-17, and IL-22, dendritic cells producing TNFα and IFNα, and other immune cells including neutrophils and mast cells. Keratinocytes respond to different cytokine signals orchestrating innate and adaptive immune responses. In vitro studies sought to clarify the cytokine effects on keratinocytes in order to evaluate the centrality of these mediators in psoriasis pathogenesis. The aim of this review is to highlight the relevance of this peculiar in vitro approach in investigating cytokine effects on skin or multilayered epidermis...
January 26, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28122092/a-review-of-brodalumab-an-il-17-receptor-antagonist-for-moderate-to-severe-plaque-psoriasis
#17
Y Tong, A J Peranteau, Z Nawas, S K Tyring
Psoriasis is a chronic immune-mediated inflammatory disease with epidermal hyperplasia that affects 2-3% of the population. Interleukin (IL)-17 signaling has a central role in its pathogenesis. Brodalumab is a monoclonal antibody that neutralizes IL-17 receptor type A. Brodalumab is highly effective in the reversal of psoriatic phenotype and gene expression patterns.
January 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28122069/interleukin-23-helper-t-cell-17-axis-as-a-treatment-target-for-pityriasis-rubra-pilaris
#18
Laurence Feldmeyer, Alessio Mylonas, Olivier Demaria, Anna Mennella, Nikhil Yawalkar, Emmanuel Laffitte, Daniel Hohl, Michel Gilliet, Curdin Conrad
Importance: Treatment of pityriasis rubra pilaris (PRP) is solely based on its resemblance to psoriasis rather than any knowledge of its pathomechanism. Insight into pathogenic mediators of inflammation is essential for targeted and valid treatment options that could replace previous serendipitous therapeutic approaches in refractory PRP. Objective: To determine whether blockade of the interleukin 23-helper T cell 17 (IL-23-TH17) pathway with ustekinumab represents an efficacious and, based on its proinflammatory cytokine profile, targeted treatment option in PRP...
January 25, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28117878/siramesine-causes-preferential-apoptosis-of-mast-cells-in-skin-biopsies-from-psoriatic-lesions
#19
E Hagforsen, M Lampinen, A Paivandy, S Weström, H Velin, S Öberg, G Pejler, O Rollman
BACKGROUND: Skin mast cells are implicated as detrimental effector cells in various inflammatory skin diseases such as contact eczema, atopic dermatitis and psoriasis. Selective reduction of cutaneous mast cells, e.g. by inducing targeted apoptosis, might prove a rational and efficient therapeutic strategy in dermatoses negatively influenced by mast cells. OBJECTIVES: The objective of the present study was to evaluate whether a lysosomotropic agent such as siramesine can cause apoptosis of mast cells present in psoriatic lesions...
January 24, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28110689/cannabinoids-possible-agents-for-treatment-of-psoriasis-via-suppression-of-angiogenesis-and-inflammation
#20
Amir Hossein Norooznezhad, Fatemeh Norooznezhad
Psoriasis is a chronic skin disease also affecting other sites such as joints. This disease highly depends on inflammation and angiogenesis as well as other pathways. At each step of the psoriasis molecular pathway, different inflammatory cytokines and angiogenic growth factors are involved such as hypoxia inducible factor-1 α (HIF-1 α), vascular endothelial growth factor (VEGF), matrix metalo proteinases (MMPs), basic fibroblast growth factor (bFGF), Angiopoitin-2, interleukin-8 (IL-8), IL-17, and IL-2. Beside the mentioned growth factors and cytokines, cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which play roles in both angiogenesis and inflammation are also involved in the pathogenesis...
February 2017: Medical Hypotheses
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