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https://www.readbyqxmd.com/read/29331587/il-23-il-17-immune-axis-in-guillain-barr%C3%A3-syndrome-exploring-newer-vistas-for-understanding-pathobiology-and-therapeutic-implications
#1
REVIEW
Monojit Debnath, Madhu Nagappa, Geetanjali Murari, Arun B Taly
Guillain Barré Syndrome (GBS) is a severe disorder of the peripheral nervous system with an inadequately known etiopathology. It is a post infectious immune mediated disorder, characterized by autoantibody production, complement activation as well as T reactivity against gangliosides. However, the precise etiopathogenesis remains poorly understood in a majority of the patients. Th17 cells, a recently identified lineage of Th cells have emerged as a predominant inducer of autoimmunity and inflammation in various immunological disorders...
January 10, 2018: Cytokine
https://www.readbyqxmd.com/read/29330562/influence-of-genetic-polymorphisms-of-il23r-stat3-il12b-and-stat4-on-the-risk-of-aplastic-anemia-and-the-effect-of-immunosuppressive-therapy
#2
Li Zhao, Huanling Zhu, Bing Han, Lixin Wang, Yuming Sun, Xiaojun Lu, Chunyan Huang, Bin Tan, Chunxia Chen, Li Qin
Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls...
January 12, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29330320/cutting-edge-homeostasis-of-innate-lymphoid-cells-is-imbalanced-in-psoriatic-arthritis
#3
Alina Soare, Stefanie Weber, Lisa Maul, Simon Rauber, Ana Maria Gheorghiu, Markus Luber, Ismail Houssni, Arnd Kleyer, Gero von Pickardt, Manuel Gado, David Simon, Jürgen Rech, Georg Schett, Jörg H W Distler, Andreas Ramming
Innate lymphoid cells (ILC) have a high potency for cytokine production independent of specific Ag stimulation. Imbalance of ILC subsets may influence cytokine production in humans and hence be associated with the development of inflammatory disease. Evidence for an imbalance of ILC homeostasis in human disease, however, is very limited to date. In this study we show that psoriatic arthritis (PsA), a severe disease of the joints depending on the activation of the IL-23/IL-17 pathway, is characterized by a skewed ILC homeostasis...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29328397/aberrant-expression-of-il-23-il-23r-in-patients-with-breast-cancer-and-its-clinical-significance
#4
Shuhai Sheng, Jinji Zhang, Jianzhong Ai, Xueli Hao, Ruishen Luan
Breast cancer tissues and adjacent tissues were collected from 32 patients who were treated in The Third Hospital of Chengde City. Reverse transcription‑quantitative polymerase chain reaction results demonstrated that, compared with the adjacent tissues, interleukin (IL)‑23/IL‑23 receptor (R) gene expression levels were notably higher in breast cancer tissues. Furthermore, IL‑23 and IL‑23R expression levels were positively correlated with patients' tumor size, TNM stage and metastasis. Recombinant human (rh) IL‑23 (10 ng/ml) was used for the stimulation of the MCF‑7 cell line...
January 12, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29327456/discovery-and-characterization-of-cd12681-a-potent-ror%C3%AE-inverse-agonist-preclinical-candidate-for-the-topical-treatment-of-psoriasis
#5
Gilles Ouvry, Nicolas Atrux-Tallau, Franck Bihl, Aline Bondu, Claire Bouix-Peter, Isabelle Carlavan, Olivier Christin, Marie-Josée Cuadrado, Claire Defoin-Platel, Sophie Deret, Denis Duvert, Christophe Feret, Mathieu Forissier, Jean-François Fournier, David Froude, Fériel Hacini-Rachinel, Craig Steven Harris, Catherine Hervouet, Hélène Huguet, Guillaume Lafitte, Anne-Pascale Luzy, Branislav Musicki, Danielle Orfila, Benjamin Ozello, Coralie Pascau, Jonathan Pascau, Véronique Parnet, Guillaume Peluchon, Romain Pierre, David Piwnica, Catherine Raffin, Patricia Rossio, Delphine Spiesse, Nathalie Taquet, Etienne Thoreau, Rodolphe Vatinel, Emmanuel Vial, Laurent François Hennequin
With possible implications in multiple autoimmune diseases, the retinoic acid receptor-related orphan receptor RORγ has become a very sought-after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated with the discovery of CD12681 (compound 14; N-(2,4-dimethylphenyl)-N-isobutyl-2-oxo-1-((tetrahydro-2H-pyran-4-yl)methyl)-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide), a potent inverse agonist with in vivo activity in an IL-23 induced skin inflammation model in mouse...
January 12, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29324391/sirna-mediated-c-rel-knockdown-ameliorates-collagen-induced-arthritis-in-mice
#6
Tingting Fan, Fuhua Zhong, Ruiling Liu, Youhai H Chen, Ting Wang, Qingguo Ruan
Previous studies have shown that inflammatory mediators involved in the development of rheumatoid arthritis (RA) are regulated by the Rel/nuclear factor-κB (Rel/NF-κB) transcription factor family. c-Rel, a member of the Rel/NF-κB family that is preferentially expressed by immune cells, is a risk factor for several inflammatory diseases including RA. In the current study, we investigated whether targeting c-Rel can be used to treat collagen-induced arthritis, an animal model for RA. c-Rel specific siRNA (siRel) delivered by nanoparticles was used to knockdown the expression of c-Rel...
January 8, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29320816/il-12-and-il-23-production-in-toxoplasma-gondii-or-lps-treated-jurkat-t-cells-via-pi3k-and-mapk-signaling-pathways
#7
Hassan Ahmed Hassan Ahmed Ismail, Byung-Hun Kang, Jae-Su Kim, Jae-Hyung Lee, In-Wook Choi, Guang-Ho Cha, Jae-Min Yuk, Young-Ha Lee
IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30-60 min...
December 2017: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/29319160/macrophage-plasticity-polarization-and-function-in-health-and-disease
#8
REVIEW
Abbas Shapouri Moghaddam, Saeed Mohammadian, Hossein Vazini, Mahdi Taghadosi, Seyed-Alireza Esmaeili, Fatemeh Mardani, Bita Seifi, Asadollah Mohammadi, Jalil Tavakol Afshari, Amirhossein Sahebkar
Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro-environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro-inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN-γ, GM-CSF and produce pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, IL-12, IL-23 and TNF-α, and 2) Alternatively activated or M2 macrophages, which are anti-inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL-4 and IL-13 and produce anti-inflammatory cytokines such as IL-10 and TGF-β...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29316717/scanning-the-immunopathogenesis-of-psoriasis
#9
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
#10
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
#11
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/29314865/il-17-plays-a-role-in-rsv-induced-lung-inflammation-and-emphysema-in-elastase-and-lps-injured-mice
#12
Yohannes A Mebratu, Yohannes Tesfaigzi
Respiratory syncytial virus (RSV) is associated with enhanced progression of chronic obstructive pulmonary disease (COPD) and COPD exacerbations. However, little is known about the role of IL-17 in RSV-induced lung injury. We first investigated the role of RSV infection in enhancing mucous cell hyperplasia and airspace enlargement in the lungs of mice injured with elastase and lipopolysaccharide (E/LPS). Mice injured with E/LPS had an enhanced and prolonged neutrophilic response to RSV that was associated with decreased levels of type I IFN and increased levels of IL-17, IL-23, CXCL-1, GCSF and CXCL-5 and MMP-9...
January 9, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29307992/fructo-oligosaccharide-intensifies-visceral-hypersensitivity-and-intestinal-inflammation-in-a-stress-induced-irritable-bowel-syndrome-mouse-model
#13
Bin-Rui Chen, Li-Jun Du, Hui-Qin He, John J Kim, Yan Zhao, Ya-Wen Zhang, Liang Luo, Ning Dai
AIM: To determine whether fructo-oligosaccharide (FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids (SCFA) in an irritable bowel syndrome (IBS) mouse model. METHODS: Mice were randomly assigned to daily oral gavage of saline solution with or without FOS (8 g/kg body weight) for 14 d. Mice were further assigned to receive either daily one-hour water avoidance stress (WAS) or sham-WAS for the first 10 d. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was evaluated...
December 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29299984/biologic-therapy-in-psoriasis-part-ii-efficacy-and-safety-of-new-treatment-targeting-il23-il-17-pathways
#14
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/29296775/th17-immune-microenvironment-in-epstein-barr-virus-negative-hodgkin-lymphoma-implications-for-immunotherapy
#15
Amy S Duffield, Maria Libera Ascierto, Robert A Anders, Janis M Taube, Alan K Meeker, Shuming Chen, Tracee L McMiller, Neil A Phillips, Haiying Xu, Aleksandra Ogurtsova, Alan E Berger, Drew M Pardoll, Suzanne L Topalian, Richard F Ambinder
Classical Hodgkin lymphoma (CHL) is a neoplasm characterized by robust inflammatory infiltrates and heightened expression of the immunosuppressive PD-1/PD-L1 pathway. Although anti-PD-1 therapy can be effective in >60% of patients with refractory CHL, improved treatment options are needed for CHLs which are resistant to anti-PD-1 or relapse after this form of immunotherapy. A deeper understanding of immunologic factors in the CHL microenvironment might support the design of more effective treatment combinations based on anti-PD-1...
July 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296188/alterations-in-the-mucosa-associated-fungal-microbiota-in-patients-with-ulcerative-colitis
#16
Xinyun Qiu, Jingjing Ma, Chunhua Jiao, Xiaqiong Mao, Xiaojing Zhao, Meijiao Lu, Kai Wang, Hongjie Zhang
Background: Fungi colonize the human gut and might play a key role in the pathogenesis of ulcerative colitis (UC). However, studies on the fungal composition in the gut (especially adhering to the intestinal mucosa) of UC patients is limited. Results: The number of fungi decreased significantly in inflamed mucosa compared with that in HS mucosa. Fifteen major genera were examined, among which Wickerhamomyces, unidentified genus of Saccharomycetales, Aspergillus, Sterigmatomyces, and Candida showed increasing trends, whereas Exophiala, Alternaria, Emericella, Epicoccum, Acremonium, Trametes, and Penicillium showed decreasing trends in UC patients compared to the HS...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295520/the-origin-of-skin-dendritic-cell-network-and-its-role-in-psoriasis
#17
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/29288381/modulation-of-the-il-23-il-17-axis-by-fenofibrate-ameliorates-the-ovalbumin-lipopolysaccharide-induced-airway-inflammation-and-bronchial-asthma-in-rats
#18
Samah M Elaidy, Soha S Essawy, Mona A Hussain, Mohamed K El-Kherbetawy, Eman R Hamed
The overlapping between asthmatic subtypes, including both CD4+ T helper (TH)2 and TH17 cells, is found in the natural course of allergic asthma, especially in exacerbations and severe and insensitive forms to steroids, which are in need of new molecular therapies. In the TH2-subset mediated asthma, fenofibrate displays therapeutic promises, besides evidenced therapeutic effects on TH17-mediated colitis and myocarditis. Therefore, the effects of fenofibrate versus dexamethasone on IL-23/IL-17 axis in ovalbumin (OVA)/lipopolysaccharide (LPS)-induced airway inflammation and bronchial asthma in rats were explored...
December 30, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29287995/structural-activation-of-pro-inflammatory-human-cytokine-il-23-by-cognate-il-23-receptor-enables-recruitment-of-the-shared-receptor-il-12r%C3%AE-1
#19
Yehudi Bloch, Laura Bouchareychas, Romain Merceron, Katarzyna Składanowska, Lien Van den Bossche, Sammy Detry, Srinath Govindarajan, Dirk Elewaut, Filomeen Haerynck, Melissa Dullaers, Iannis E Adamopoulos, Savvas N Savvides
Interleukin-23 (IL-23), an IL-12 family cytokine, plays pivotal roles in pro-inflammatory T helper 17 cell responses linked to autoimmune and inflammatory diseases. Despite intense therapeutic targeting, structural and mechanistic insights into receptor complexes mediated by IL-23, and by IL-12 family members in general, have remained elusive. We determined a crystal structure of human IL-23 in complex with its cognate receptor, IL-23R, and revealed that IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain...
December 21, 2017: Immunity
https://www.readbyqxmd.com/read/29287831/systemic-inflammation-in-asocial-btbr-t-tf-j-mice-predisposes-them-to-increased-psoriatic-inflammation
#20
Ahmed Nadeem, Sheikh F Ahmad, Ahmad M El-Sherbeeny, Naif O Al-Harbi, Saleh A Bakheet, Sabry M Attia
Autistic Spectrum disorder (ASD) is a neurobehavioral disorder characterized by defects in communication skills leading to restricted sociability. ASD has immense dysregulation in immune responses which is thought to affect neuronal system and thus behavior. ASD patients and BTBR T+ tf/J (BTBR) autistic mice have increased systemic inflammation due to dysfunction in innate and adaptive immune responses. Recent studies suggest that ASD patients are associated with several co-morbid autoimmune disorders including psoriasis...
December 26, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
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