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IL-17 and psoriasis

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https://www.readbyqxmd.com/read/29316717/scanning-the-immunopathogenesis-of-psoriasis
#1
REVIEW
Andrea Chiricozzi, Paolo Romanelli, Elisabetta Volpe, Giovanna Borsellino, Marco Romanelli
Psoriasis is a chronic inflammatory skin disease, the immunologic model of which has been profoundly revised following recent advances in the understanding of its pathophysiology. In the current model, a crosstalk between keratinocytes, neutrophils, mast cells, T cells, and dendritic cells is thought to create inflammatory and pro-proliferative circuits mediated by chemokines and cytokines. Various triggers, including recently identified autoantigens, Toll-like receptor agonists, chemerin, and thymic stromal lymphopoietin may activate the pathogenic cascade resulting in enhanced production of pro-inflammatory and proliferation-inducing mediators such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-23, IL-22, interferon (IFN)-α, and IFN-γ by immune cells...
January 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29316631/psoriasis-a-stat3-centric-view
#2
REVIEW
Enzo Calautti, Lidia Avalle, Valeria Poli
Signal Transducer and Activator of Transcription (STAT)3 has recently emerged as a key player in the development and pathogenesis of psoriasis and psoriatic-like inflammatory conditions. Indeed, STAT3 hyperactivation has been reported in virtually every cell type involved in disease initiation and maintenance, and this factor mediates the signal of most cytokines that are involved in disease pathogenesis, including the central Interleukin (IL)-23/IL-17/IL-22 axis. Despite the recent availability of effective biological agents (monoclonal antibodies) against IL-17 and IL-23, which have radically changed the current standard of disease management, the possibility of targeting either STAT3 itself or, even better, the family of upstream activators Janus kinases (JAK1, 2, 3, and TYK2) offers additional therapeutic options...
January 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29315555/autoimmunity-and-autoimmune-comorbidities-in-psoriasis
#3
REVIEW
Kazuhisa Furue, Takamichi Ito, Gaku Tsuji, Takafumi Kadono, Takeshi Nakahara, Masutaka Furue
Psoriasis is characterized by widespread scaly erythematous plaques that cause significant physical and psychological burdens for the affected individuals. Accelerated inflammation driven by the TNF-α/IL-23/IL-17 axis is now known to be the major mechanism of the development of psoriasis. In addition, psoriasis has an autoimmune nature that manifests as autoreactive T cells and is comorbid with other autoimmune diseases, such as autoimmune bullous diseases, vitiligo, alopecia and thyroiditis. In this article, we review the recent topics on autoimmunity and autoimmune comorbidities in psoriasis...
January 9, 2018: Immunology
https://www.readbyqxmd.com/read/29302052/the-act1-d10n-missense-variant-impairs-cd40-signaling-in-human-b-cells
#4
Ning Yu, Sylviane Lambert, Joshua Bornstein, Rajan P Nair, Charlotta Enerbäck, James T Elder
The TRAF3IP2 gene resides within one of at least 63 psoriasis susceptibility loci and encodes Act1, an adapter protein involved in IL-17 receptor and CD40 signaling pathways. TRAF3IP2 is distinctive (among <10% of candidate susceptibility genes) in that a strongly disease-associated variant encodes a missense SNP predicted to be functionally relevant (SNP rs33980500 C/T encoding Act1 pD10N). As assessed by flow cytometry, Act1 protein was expressed at the highest levels in monocytes, with lower levels in T-cells and B-cells...
January 5, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29299984/biologic-therapy-in-psoriasis-part-ii-efficacy-and-safety-of-new-treatment-targeting-il23-il-17-pathways
#5
E Molinelli, A Campanati, Giulia Ganzetti, V Brisigotti, A Offidani
BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disorder that is estimated to affect 2-3% of the general population. The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. METHODS: Biologics licensed for psoriasis include the TNFα inhibitors (infliximab, adalimumab, etanercept), the interleukin (IL)-12/23 monoclonal antibody (ustekinumab), and IL-17 inhibitor (secukinumab, ixekizumab). RESULTS: In this section, we analyse the role of IL-12, IL-23, and IL-17 in psoriasis and evaluated the efficacy and safety of biologic therapies targeting this cytokine...
January 3, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29295585/topical-application-of-glycolipids-from-isochrysis-galbana-prevents-epidermal-hyperplasia-in-mice
#6
Azahara Rodríguez-Luna, Elena Talero, María Del Carmen Terencio, María Luisa González-Rodríguez, Antonio M Rabasco, Carolina de Los Reyes, Virginia Motilva, Javier Ávila-Román
Chronic inflammatory skin diseases such as psoriasis have a significant impact on society. Currently, the major topical treatments have many side effects, making their continued use in patients difficult. Microalgae have emerged as a source of bio-active molecules such as glycolipids with potent anti-inflammatory properties. We aimed to investigate the effects of a glycolipid (MGMG-A) and a glycolipid fraction (MGDG) obtained from the microalga Isochrysis galbana on a TPA-induced epidermal hyperplasia murine model...
December 25, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29295520/the-origin-of-skin-dendritic-cell-network-and-its-role-in-psoriasis
#7
REVIEW
Tae-Gyun Kim, Sung Hee Kim, Min-Geol Lee
Dendritic cells (DCs) are heterogeneous groups of innate immune cells, which orchestrate immune responses by presenting antigens to cognate T cells and stimulating other types of immune cells. Although the term 'DCs' generally represent highly mixed subsets with functional heterogeneity, the classical definition of DCs usually denotes conventional DCs (cDCs). Skin contains a unique DC network mainly composed of embryo precursor-derived epidermal Langerhans cells (LCs) and bone marrow-derived dermal cDCs, which can be further classified into type 1 (cDC1) and type 2 (cDC2) subsets...
December 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29288651/unopposed-il-36-activity-promotes-clonal-cd4-t-cell-responses-with-il-17a-production-in-generalized-pustular-psoriasis
#8
Akiko Arakawa, Sigrid Vollmer, Petra Besgen, Adrian Galinski, Burkhard Summer, Yoshio Kawakami, Andreas Wollenberg, Klaus Dornmair, Michael Spannagl, Thomas Ruzicka, Peter Thomas, Jörg C Prinz
Generalized pustular psoriasis (GPP) is the most severe psoriasis variant. Mutations in the IL-36 antagonist IL36RN, in CARD14 or AP1S3 provide genetic evidence for autoinflammatory aetiology but cannot explain its pathogenesis completely. Here we demonstrate that unopposed IL-36 signalling promotes antigen-driven and likely pathogenic T-helper 17 (Th17) responses in GPP. We observed that CD4+ T cells in blood and skin lesions of GPP patients were characterized by intense hyperproliferation, production of the GPP key mediator, IL-17A, and highly restricted T-cell receptor (TCR) repertoires with identical T-cell clones in blood and skin lesions indicating antigen-driven T-cell expansions...
December 27, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29260411/malignancy-risk-and-recurrence-with-psoriasis-and-its-treatments-a-concise-update
#9
REVIEW
Shamir Geller, Haoming Xu, Mark Lebwohl, Beatrice Nardone, Mario E Lacouture, Meenal Kheterpal
Psoriasis is a common inflammatory cutaneous disease that affects approximately 120 million people worldwide. Systemic treatments have significantly improved disease burden, but concerns persist regarding their association with increased risk of malignancy. Patients with psoriasis have a slightly elevated baseline risk of lymphoproliferative diseases. Studies on methotrexate and cyclosporine, as well as older biological agents such as tumor necrosis factor inhibitors, have found no increased risk of non-cutaneous solid tumors; however, positive associations between cutaneous squamous cell carcinomas and certain therapies have been found...
December 19, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/29246798/dlx3-dependent-stat3-signaling-in-keratinocytes-regulates-skin-immune-homeostasis
#10
Shreya Bhattacharya, Jin-Chul Kim, Youichi Ogawa, Gaku Nakato, Veronica Nagle, Stephen R Brooks, Mark C Udey, Maria I Morasso
Epidermal specific deletion of the homeobox transcription regulator DLX3 disrupts keratinocyte differentiation and results in an IL-17-linked psoriasis-like skin inflammation. To identify the epidermal initiating signals produced by DLX3-null keratinocytes, we performed acute deletion of DLX3 in adult epidermis using a tamoxifen-inducible Krt14-cre/ERT system. K14CreERT;DLX3fl/fl (icKO) skin exhibited dysregulated expression of differentiation-associated genes, upregulation of proinflammatory cytokines, and accumulation of Langerhans cells and macrophages within 3 days of tamoxifen-induced DLX3 ablation...
December 12, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29230331/the-successful-treatment-of-a-case-of-linear-psoriasis-with-ixekizumab
#11
Sara Ghoneim, Alvaro J Ramos-Rodriguez, Fernando Vazquez de Lara, Lauren Bonomo
Linear psoriasis is an unusual clinical variation of psoriasis that manifests segmentally along the lines of Blaschko. A major differential diagnosis is inflammatory linear verrucous epidermal nevus (ILVEN). The treatment of linear psoriasis is often challenging, with inadequate response to biological agents reported in the literature. We report a case of a 25-year-old African-American female who presented with asymptomatic hyperkeratotic papules along the lines of Blaschko and was subsequently diagnosed with linear psoriasis...
2017: Case Reports in Dermatological Medicine
https://www.readbyqxmd.com/read/29228429/peripheral-blood-cd8-t-cell-profiles-in-patients-with-psoriatic-arthritis-a-cross-sectional-case-control-study
#12
E Colombo, G Galleri, G L Erre, C Piras, G Biondi, L Taras, A Zinellu, A A Mangoni, R Manetti, M Montesu, G Passiu
OBJECTIVE: While CD4+ T-cells are traditionally regarded as the main pathogenic T-cell subpopulation in psoriatic arthritis (PsA), the role of circulating CD8+ T-cells remains poorly characterized. We evaluated the differential representation of CD8+ T-cell subpopulations in peripheral blood (PB) of PsA patients. PATIENTS AND METHODS: CD8+IL-17+, CD8+IFNγ+ and CD8+IL-17-IL-22+ T-cells were evaluated by flow-cytometry in 25 consecutive PsA patients, 7 rheumatoid arthritis (RA) patients, 16 patients with psoriasis, and 26 healthy controls (HC)...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29226369/safety-of-biologics-in-psoriasis
#13
REVIEW
Masahiro Kamata, Yayoi Tada
The advent of biologics brought a paradigm shift in ways to treat psoriatic patients because they have dramatic efficacy. At the same time, safety concerns about biologics have been raised. In this paper, we focus on the safety profile of biologics for psoriasis. As of 2017, six biologics are available in Japan. Two tumor necrosis factor-α inhibitors; infliximab and adalimumab, one anti-interleukin (IL)-12/23p40 antibody; ustekinumab, and IL-17 inhibitors; secukinumab, ixekizumab and brodalumab. Secukinumab and ixekizumab are anti-IL-17A antibodies...
December 10, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/29222947/safety-and-efficacy-of-guselkumab-in-japanese-patients-with-moderate-to-severe-plaque-psoriasis-a-randomised-placebo-controlled-ascending-dose-study
#14
O Nemoto, K Hirose, S Shibata, K Li, H Kubo
BACKGROUND: The Interlukin-23 (IL-23)/Interlukin-17 (IL-17) pathway is central in the pathogenesis of psoriasis. The favourable efficacy and safety of guselkumab, an IL-23 specific monoclonal antibody, has been demonstrated in global Phase 3 studies of plaque psoriasis. OBJECTIVES: To evaluate the safety, efficacy and pharmacokinetics of a single-dose subcutaneous guselkumab in Japanese patients with moderate-to-severe plaque psoriasis. METHODS: Patients with ≥ 10% of total body surface area (BSA) involvement and a Psoriasis Area and Severity Index (PASI) ≥12 were randomised (5:1) to receive guselkumab or placebo in 4 cohorts of this double-blind, placebo-controlled, single ascending dose, single-centre study...
December 9, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29222824/elevated-levels-of-the-antimicrobial-peptide-ll-37-in-hidradenitis-suppurativa-are-associated-with-a-th1-th17-immune-response
#15
R Thomi, C Schlapbach, N Yawalkar, D Simon, D Yerly, R E Hunger
Hidradenitis suppurativa (HS) is an inflammatory skin disease with poorly understood immunopathogenic mechanisms. LL-37 is an antimicrobial peptide, which is transcribed from the CAMP (cathelicidin antimicrobial peptide) gene. Previous reports showed upregulated levels of CAMP and LL-37 in HS lesions and therefore the aim of this study was to compare levels of LL-37 in HS to other inflammatory skin diseases and to establish immunomodulatory functions of LL-37 in HS. We confirm an upregulation of the LL-37 peptide in lesional HS skin with comparable levels as in psoriasis patients and are able to positively correlate the presence of LL-37 in HS with the presence of T cells, macrophages, neutrophils, IFNγ, IL-17, IL-23, TNFα, IL-32 and IL-1β...
December 8, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/29220875/interleukin-21-receptor-signaling-is-not-critically-required-for-imiquimod-induced-psoriasiform-dermatitis-in-mice
#16
Hee Joo Kim, Sung Hee Kim, Tae-Gyun Kim, Je Yun Park, Minseok Lee, Dae Suk Kim, Min-Geol Lee
Psoriasis is largely mediated by interleukin (IL)-23/ T helper (Th) 17 axis, and IL-21 is a pleiotropic cytokine expressed by Th17 cells. Despite previously reported possible pathogenic roles of IL-21 in human psoriasis, we found that IL-21 receptor (IL-21R) signaling was not crucial for imiquimod-induced psoriatic inflammation, using IL-21R-/- mice. The severity of imiquimod-induced psoriatic manifestation and pro-inflammatory Th17 cytokine levels, IL-17A-producing γδ T cells and CD4+ T cells, and in vitro IL-17A production by γδ T cells after IL-23 stimulation was comparable between wild-type and IL-21R-/- mice...
December 8, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/29203226/innately-versatile-%C3%AE-%C3%AE-17%C3%A2-t-cells-in-inflammatory-and-autoimmune-diseases
#17
REVIEW
Pedro H Papotto, Annika Reinhardt, Immo Prinz, Bruno Silva-Santos
IL-17-producing γδ (γδ17) T cells form a versatile subset of cells that respond rapidly to innate stimuli and support the pro-inflammatory functions of different myeloid and lymphoid lineages, being particularly critical in the early stages of inflammatory and autoimmune responses. In mice, under homeostatic conditions, these innate-like lymphocytes are pre-programmed in the fetal thymus, through an intricate process involving both T cell receptor-dependent and -independent signals, which allows them to readily produce IL-17 upon stimulation...
December 1, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29194565/impaired-langerhans-cell-migration-in-psoriasis-is-due-to-an-altered-keratinocyte-phenotype-induced-by-interleukin-17
#18
L H Eaton, K T Mellody, S M Pilkington, R J Dearman, I Kimber, C E M Griffiths
Psoriasis is a common skin condition driven by increased expression of interleukin (IL)-17. Langerhans' cells (LC) are epidermal dendritic cells that regulate cutaneous immune responses. Within uninvolved skin of patients with psoriasis, LC display impaired migration from the epidermis. Here the role of keratinocytes (KC) in the regulation of LC function, and the response of KC to IL-17 has been investigated. Keratinocytes were cultured from the uninvolved skin of psoriasis patients and healthy individuals with or without IL-17 treatment and the conditioned medium examined for its ability to alter LC function in an ex vivo human skin explant model...
December 1, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29193791/il-35-recombinant-protein-reverses-inflammatory-bowel-disease-and-psoriasis-through-regulation-of-inflammatory-cytokines-and-immune-cells
#19
Yuan Wang, Ying Mao, Junfeng Zhang, Gang Shi, Lin Cheng, Yi Lin, Yiming Li, Xiaomei Zhang, Yujing Zhang, Xiaolei Chen, Jie Deng, Xiaolan Su, Lei Dai, Yang Yang, Shuang Zhang, Dechao Yu, Yuquan Wei, Hongxin Deng
Interleukin-35 (IL-35), a member of the IL-12 family, functions as a new anti-inflammatory factor involved in arthritis, psoriasis, inflammatory bowel disease (IBD) and other immune diseases. Although IL-35 can significantly prevent the development of inflammation in many diseases, there have been no early studies accounting for the role of IL-35 recombinant protein in IBD and psoriasis. In this study, we assessed the therapeutic potential of IL-35 recombinant protein in three well-known mouse models: the dextransulfate sodium (DSS)-induced colitis mouse model, the keratin14 (K14)-vascular endothelial growth factor A (VEGF-A)-transgenic (Tg) psoriasis mouse model and the imiquimod (IMQ)-induced psoriasis mouse model...
November 29, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29187009/ixekizumab-an-anti-il-17a-monoclonal-antibody-for-the-treatment-of-psoriatic-arthritis
#20
Eric Toussirot
Psoriatic arthritis (PsA) is an inflammatory rheumatic disease that manifests itself with synovitis, dactylitis, enthesitis and also axial involvement. Interleukin-17A has been identified as a master cytokine in the inflammatory response and pathogenesis of PsA and spondyloarthritis in general. Ixekizumab is a new humanized monoclonal antibody that blocks the biological activity of IL-17A. This biological agent has previously demonstrated a high level of efficacy in psoriasis. Areas covered: This review discusses the basic immunology of the IL-17 cytokine family, the contribution of IL-17A to the immunopathogenesis of PsA, the clinical trials that evaluated ixekizumab in patients with PsA (SPIRIT program) and the safety of this agent...
January 2018: Expert Opinion on Biological Therapy
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