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Il-23 and psoriasis

Insa Joost, Johannes Steinfurt, Philipp T Meyer, Winfried V Kern, Siegbert Rieg
BACKGROUND: Ustekinumab (Stelara®), a human monoclonal antibody targeting the p40-subunit of interleukin (IL)-12 and IL-23, is indicated for moderate to severe plaque psoriasis and psoriatic arthritis. In large multicenter, prospective trials assessing efficacy and safety of ustekinumab increased rates of severe infections have not been observed so far. CASE PRESENTATION: Here, we report the case of a 64-year old woman presenting with chills, pain and swelling of her right foot with dark maculae at the sole, and elevated inflammatory markers...
October 20, 2016: BMC Infectious Diseases
Robert Bissonnette, Judilyn Fuentes-Duculan, Shunya Mashiko, Xuan Li, Kathleen M Bonifacio, Inna Cueto, Mayte Suárez-Fariñas, Catherine Maari, Chantal Bolduc, Simon Nigen, Marika Sarfati, James G Krueger
BACKGROUND: Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis, which has significant negative impact on quality of life. The cellular and molecular inflammatory pathways involved in PPPP have not been well studied. OBJECTIVE: Study the expression of cytokines and chemokines involved in the IL-17/IL-23 axis in palmoplantar pustular psoriasis and other difficult to treat psoriasis areas (palms, scalp, elbows and lower legs). METHODS: Skin biopsies were performed on a total of 80 patients with PPPP, non-pustular palmoplantar psoriasis (NPPPP), or psoriasis located on elbows, knees and scalp as well as 10 healthy subjects...
September 29, 2016: Journal of Dermatological Science
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
J Loget, J Plee, F Antonicelli, P Bernard
Predisposing factors for bullous pemphigoid (BP), the most common autoimmune blistering disease, include neurological disorders, chronic use of certain drugs (spironolactone, loop diuretics, psycholeptics).(1) The coexistence of psoriasis with classical BP is occasionally observed, whereas half of the patient population with anti-laminin γ1 pemphigoid of Japanese origin have coexisting psoriasis.(2-3) We report for the first time a case of relapsing BP associated with psoriasis, in which both dermatoses completely disappeared after treatment with ustekinumab, a monoclonal antibody that targets the p40 subunit of IL-12/23...
October 12, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Mikiro Takaishi, Masayuki Ishizaki, Keisuke Suzuki, Takashi Isobe, Takaichi Shimozato, Shigetoshi Sano
BACKGROUND: Targeting the IL-17 pathway represents a highly effective strategy for the treatment of psoriasis, using antibodies against IL-17A and IL-17 receptor, suggesting that Th17 cells essentially contribute to development of psoriasis. Th17 differentiation depends on the key transcription factor, RORγt. OBJECTIVE: To develop a novel RORγt antagonist which is effective on psoriasis via oral administration. METHODS: A chemical library was screened using cell-based high-throughput methods, luciferase reporter assay, competitive binding assay, and T cell differentiation assay...
October 3, 2016: Journal of Dermatological Science
M Galluzzo, S D'Adamio, L Bianchi, M Talamonti
Psoriasis is a complex disease in which the alteration of the IL-23/Th17 axis appears to be crucial for its pathogenic mechanisms, and anti-IL17 agents are rapidly becoming important therapeutic tools. Brodalumab, a fully human Chinese hamster ovary cell-derived immunoglobulin G2 (IgG2) anti-IL-17RA monoclonal antibody, is currently the most-developed treatment that binds to the IL-17RA. The authors review and provide updates of efficacy and safety by several studies on brodalumab. Areas covered: A PubMed search was performed for relevant literature...
October 10, 2016: Expert Review of Clinical Immunology
David A Ewald, Shinji Noda, Margeaux Oliva, Thomas Litman, Saeko Nakajima, Xuan Li, Hui Xu, Peter Scheipers, Naila Svitacheva, Tord Labuda, James G Krueger, Mayte Suárez-Fariñas, Kenji Kabashima, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) is caused by a complex interplay between immune and barrier abnormalities. Murine models of AD are essential for preclinical assessments of new treatments. While many models have been used to simulate AD, their transcriptomic profiles are not fully understood, and a comparison of these models with the human AD transcriptomic fingerprint is lacking. OBJECTIVE: We sought to evaluate the transcriptomic profiles of six common murine models and determine how they relate to human AD skin...
October 1, 2016: Journal of Allergy and Clinical Immunology
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
Wang Sin Gina Tan, Stephen Kelly, Constantino Pitzalis
Biologic therapy has revolutionized treatment pathways in psoriatic joint and skin disease. It has also provided a useful tool with which pathological pathways of this condition may be explored. Areas Covered: This review presents data on the clinical and biological effects of targeted therapy in psoriatic arthritis and psoriasis. Therapeutic agents covered include inhibitors of TNFα, inhibitors of the IL-23/IL-17 axis and inhibitors of intracellular small molecules involved in the transduction of the inflammatory signal...
October 3, 2016: Expert Review of Clinical Immunology
Jaehwan Kim, James G Krueger
Psoriasis vulgaris, affecting the skin, is one of the most common organspecific autoimmune diseases in humans. Until recently, psoriasis was treated by agents or approaches discovered largely through serendipity. Many of the available drugs were inherently quite toxic when used as continuous treatment for many years in this chronic disease. However, an increasing understanding of disease-specific immune pathways has spurred development of pathway-targeted therapeutics during the past decade. Psoriasis is now the most effectively treated human autoimmune disease, with high-level clinical improvements possible in ∼90% of patients using a new generation of drugs that selectively target the IL-23/Type 17 T cell axis...
September 23, 2016: Annual Review of Medicine
Sirish K Ippagunta, Ruchika Gangwar, David Finkelstein, Peter Vogel, Stephane Pelletier, Sebastien Gingras, Vanessa Redecke, Hans Häcker
Psoriasis is a chronic inflammatory skin disease with a clear genetic contribution, characterized by keratinocyte proliferation and immune cell infiltration. Various closely interacting cell types, including innate immune cells, T cells, and keratinocytes, are known to contribute to inflammation. Innate immune cells most likely initiate the inflammatory process by secretion of IL-23. IL-23 mediates expansion of T helper 17 (Th17) cells, whose effector functions, including IL-17A, activate keratinocytes. Keratinocyte activation in turn results in cell proliferation and chemokine expression, the latter of which fuels the inflammatory process through further immune cell recruitment...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Lazaros I Sakkas, Dimitrios P Bogdanos
Psoriatic arthritis (PsA) is a psoriasis (Ps)-associated inflammatory joint disease that affects peripheral joints, entheses, spine, and eyes. PsA and Ps are likely to be the same disease. PsA develops in nearly 70% of patients with Ps, and the hallmark of the disease is bone erosions and bone formation. Both innate and adaptive immunity appear to contribute to pathogenesis of PsA and Ps. Trauma may be a trigger factor for both PsA and Ps. The same T cell clones were reported to be present in both synovial tissues and skin lesions suggesting that a common antigen drives T cell immune response in the joints and skin lesions of patients with PsA...
September 22, 2016: Autoimmunity Reviews
Tony J Kenna, Aimee Hanson, Mary-Ellen Costello, Matthew A Brown
Ankylosing spondylitis (AS) is a highly heritable disease for which there is a great unmet need for improved therapies. Genetics research has identified several major pathways involved in the disease, from which treatments have either now entered clinical practice or are in development. In particular, therapies targeting the IL-23 pathway were repositioned for use in AS following the discovery of multiple genes in the pathway as determinants of AS risk. Discovery of the association of aminopeptidase genes with AS, and subsequently with psoriasis, inflammatory bowel disease and other conditions, has triggered research into therapies targeting this pathway...
October 2016: Current Rheumatology Reports
Mariagrazia Granata, Evangelia Skarmoutsou, Chiara Trovato, Giulio A Rossi, Maria Clorinda Mazzarino, Fabio D'Amico
Obesity, type 1 diabetes, and psoriasis are wide-ranging health problems. Genetics, epigenetics, and environmental factors together with immune disturbances are involved in these diseases. The white adipose tissue is an active endocrine organ, secreting a wide variety of soluble mediators called adipokines that have a central role in the relationship between adipose tissue and immune system. Inflammatory cytokines, including the IL-23/IL-17 and IL-18 axes, and microRNAs are involved in many processes, including immunity and inflammation, thus having a major role in the onset of these three diseases...
September 17, 2016: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Agnieszka Wasilewska, Marta Winiarska, Małgorzata Olszewska, Lidia Rudnicka
Psoriasis is a chronic skin disease caused by the excessive secretion of inflammatory cytokines. Available therapeutic options include biologic drugs such as tumor necrosis factor alpha inhibitors and interleukin 12/23 (IL-12/23) inhibitors. The recent discovery of IL-17, which contributes to development of psoriasis, opened new possibilities for further treatment modalities. Currently, one anti-IL17 biological agent is approved for the treatment - a fully human monoclonal antibody that targets IL-17A (secukinumab)...
August 2016: Postȩpy Dermatologii i Alergologii
Kenneth B Gordon
Knowledge about the pathophysiology of psoriasis has evolved substantially in recent years, since the identification of the T helper 17 (Th17) cells. Cytokines produced by these cells appear to play major roles in psoriatic inflammation. The cytokine interleukin (IL)-23 appears to promote regulatory T cells to differentiate into Th17 cells. Available and investigational therapies act on targets within these pathways. Semin Cutan Med Surg 35(supp4):S64.
June 2016: Seminars in Cutaneous Medicine and Surgery
Jung Ki Yoo, Young-Kug Choo, Dong Hoon Kwak, Jong Min Lee, Chi-Yeon Lim, Ju-Hee Lee, Mi-Young Park, Chang-Hyun Kim
Agonistic anti-4-1BB antibodies (Abs) play a central role in immunomodulatory conditions that control the pathogenesis of immune-mediated autoimmune and allergic diseases. However, the effects of agonistic anti-4-1BB Abs have not been examined in an experimental mouse model of psoriasis. Therefore, we investigated the protective effects of agonistic anti-4-1BB Abs, using imiquimod (IMQ)-induced psoriasis-like dermatitis in mice, a condition histologically and clinically similar to human psoriasis. We found that administration of agonistic anti-4-1BB Abs (10mg/kg) significantly alleviated the severity of IMQ-induced psoriasis-like skin inflammation in mice, with reduced histologic symptoms, including inflammatory infiltration, parakeratosis, and hyperkeratosis...
October 2016: Immunology Letters
Yoshiya Tanaka
Psoriatic arthritis (PsA) is a chronic and progressive inflammatory arthritis that is common among patients with psoriasis, often resulting in permanent damage of joints and spines. Recent report indicates that the prevalence of PsA among Japanese patients with psoriasis is 14.3%, which is similar or slightly less than that of PsA in Caucasian, 6-42%. Skin disorders precede arthritis in 60-80% of Japanese patients with PsA and oligoarthritis or polyarthritis is the dominant pattern of them. The genotypic backgrounds appear different among Japanese and Caucasians...
July 2016: Clinical and Experimental Rheumatology
Shuangshuang Zhang, Xiangdong Liu, Lihong Mei, Hongfeng Wang, Fang Fang
BACKGROUND: Psoriasis is a chronic inflammatory immune disease with undefined pathogenesis. It is associated with T cells, and the IL-23/IL17 axis is believed to be crucial in the pathogenesis. The present treatments have side effects that influence the compliance of patients. Tea polyphenol is extracted from tea polyphenols, and its main active ingredient is Epigallocatechin-3-gallate (EGCG), which has been shown to have antioxidant, anti-tumor, and anti-ultraviolet radiation effects...
2016: BMC Complementary and Alternative 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
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