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IL 17 receptor B

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https://www.readbyqxmd.com/read/28818508/the-role-of-the-il-8-signaling-pathway-in-the-infiltration-of-granulocytes-into-the-livers-of-patients-with-alcoholic-hepatitis
#1
S W French, A S Mendoza, N Afifiyan, B Tillman, E Vitocruz, B A French
BACKGROUND AND AIM: IL-8 (C-X-L motif chemokine ligase 8) and CXCR2 (C-X-C-motif chemokine receptor 2) are up regulated in alcoholic hepatitis (AH) liver biopsies. One of the consequences is the attraction and chemotactic neutrophilic infiltrate seen at the AH stage of alcoholic liver disease. MATERIALS AND METHODS: Human formalin-fixed, paraffin-embedded (FFPE) liver biopsies from patients who have AH were studied by (2.1) RNA sequencing, (2.2) PCR and (2.3) semi quantitation of specific proteins in biopsy sections using immunohistochemical measurements of antibody fluorescent intensity with morphometric technology...
August 14, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28770550/association-of-the-haem-oxygenase-1-gene-with-inflammatory-bowel-disease
#2
Zhenwu Lin, Han Hao, John P Hegarty, Tony R Lin, Yunhua Wang, Leonard R Harris, He N Xu, Rongling Wu, Neal J Thomas, Joanna Floros
The anti-inflammatory genes, haem oxygenase 1 (HO-1, HMOX1) rs2071746 (unrestricted model: p = 9.07 × 10-4; recessive model: p = 4.99 × 10-4; multiplicative model: p = 0.0009; and additive model: p = 1.87 × 10-4) and interleukin-10 (IL-10) rs1800872 (dominant model: p = 0.0277) have been associated with paediatric inflammatory bowel disease. The present family-based case-trio study (n = 52) examined HO-1 gene expression in the presence of proinflammatory lipopolysaccharide and tumour necrosis factor-alpha in four B lymphocyte cell lines established from children with inflammatory bowel disease and demonstrated that mutations in IL-10 and IL-10 receptor B reduced HO-1 messenger RNA expression...
August 3, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28765121/novel-therapies-for-immune-mediated-inflammatory-diseases-what-can-we-learn-from-their-use-in-rheumatoid-arthritis-spondyloarthritis-systemic-lupus-erythematosus-psoriasis-crohn-s-disease-and-ulcerative-colitis
#3
REVIEW
Kenneth F Baker, John D Isaacs
The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide...
August 1, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28732152/secukinumab-in-the-treatment-of-psoriasis-and-psoriatic-arthritis-a-review-of-the-literature
#4
M Abrouk, J Gandy, M Nakamura, K Lee, M Brodsky, R Singh, H Zhu, B Farahnik, T Bhutani, J Koo
While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis...
July 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28684599/il-23-restoration-of-th17-effector-function-is-independent-of-il-6-and-tgf-%C3%AE-in-a-mouse-model-of-alcohol-and-burn-injury
#5
Xiaoling Li, Abigail R Cannon, Adam M Hammer, Niya L Morris, Mashkoor A Choudhry
T cells play a critical role in host defense against intestinal bacteria. We have shown that ethanol combined with burn injury suppresses Peyer's patch (PP) Th17 cytokines 1 d after injury. We assessed the mechanism of suppressed Th17 effector functions. Mice were gavaged with ethanol 4 h before burn injury and euthanized 1, 3, and 7 d after injury. Mesenteric lymph nodes (MLNs), PPs, and spleen Th1 and Th17 cytokines were assessed. A significant decrease in IL-17, IL-22, IL-2, and IFN-γ were observed in all 3 lymphoid organs 1 and 3 d after injury...
July 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28672038/t-cell-activation-and-differentiation-is-modulated-by-a-cd6-domain-1-antibody-itolizumab
#6
Usha Bughani, Arindam Saha, Anshu Kuriakose, Reshmi Nair, Ravindra B Sadashivarao, Rasika Venkataraman, Swati Patel, Anuja Tushar Deshchougule, Satish Kumar S, Enrique Montero, Harish V Pai, Dinesh V Palanivelu, Ramakrishnan Melarkode, Pradip Nair
CD6 is associated with T-cell modulation and is implicated in several autoimmune diseases. We previously demonstrated that Itolizumab, a CD6 domain 1 (CD6D1) specific humanized monoclonal antibody, inhibited the proliferation and cytokine production by T lymphocytes stimulated with anti-CD3 antibody or when co-stimulated with ALCAM. Aberrant IL-17 producing CD4+ helper T-cells (Th17) have been identified as pivotal for the pathogenesis of certain inflammatory autoimmune disorders, including psoriasis. Itolizumab has demonstrated efficacy in human diseases known to have an IL-17 driven pathogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28664612/autoimmune-arthritis-induces-paired-immunoglobulin-like-receptor-b-expression-on-cd4-t%C3%A2-cells-from-skg-mice
#7
Kathrin Rothe, Nora Raulien, Gabriele Köhler, Matthias Pierer, Dagmar Quandt, Ulf Wagner
The chronic, destructive autoimmune arthritis in SKG mice, which closely resembles human rheumatoid arthritis, is the result of self-reactive T cells escaping thymic deletion. Since the inhibitory receptor LIR-1 is up-regulated on auto-reactive T cells in human rheumatoid arthritis, the role of its murine ortholog PIR-B was investigated. Peripheral CD4(+) T cells from SKG mice were found to frequently express PIR-B, and this population produces more frequently IL-17 upon in vitro stimulation compared to PIR-B(-) cells...
June 30, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28659029/the-mixture-of-anemarrhena-asphodeloides-and-coptis-chinensis-attenuates-high-fat-diet-induced-colitis-in-mice
#8
Su-Min Lim, Hyun-Sik Choi, Dong-Hyun Kim
Anemarrhena asphodeloides (AA, family Liliaceae) inhibits macrophage activation by inhibiting IRAK1 phosphorylation and helper T (Th)17 differentiation. Coptis chinensis (CC, family Ranunculaceae), which inhibits macrophage activation by inhibiting the binding of lipopolysaccharide (LPS) on toll-like receptor 4 and inducing regulatory T (Treg) cell differentiation. The mixture of AA and CC (AC-mix) synergistically attenuates 2,4,6-trinitrobenzenesulfonic acid or dextran sulfate sodium-induced colitis in mice by inhibiting NF-[Formula: see text]B activation and regulating Th17/Treg balance...
June 28, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28654150/severe-hidradenitis-suppurativa-responding-to-treatment-with-secukinumab-a-case-report
#9
L Thorlacius, P Theut Riis, G B E Jemec
An inappropriate immunologic response to an unknown antigen has been suggested to play a role in the pathogenesis of Hidradenitis suppurativa (HS). Studies have identified elevated levels of several proinflammatory cytokines, including IL-17A and TNF-α, nominating these as possible therapeutic targets.(1) Secukinumab is an Il-17A monoclonal antibody, which binds to Il-17A and inhibits the cytokine interaction with the Il-17 receptors, inhibiting the inflammatory cascade. Here we report on a case of a 47-year-old man, with Hurley Stage III lesions at the neck, axillae, breasts, genital skin and buttocks, who had experienced only temporary benefit from different medical treatments over the years...
June 27, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28646040/il-23-limits-the-production-of-il-2-and-promotes-autoimmunity-in-lupus
#10
Hong Dai, Fan He, George C Tsokos, Vasileios C Kyttaris
The IL-23/IL-17 pathway is important in multiple autoimmune diseases, but its effect on lupus pathology remains unclear, with opposing trials in murine models of the disease. In this study, we show a disease activity-related upregulation of serum IL-23 and IL-23 receptor in patients with systemic lupus erythematosus (SLE) as compared with healthy controls. When added in SLE T cell in vitro cultures, IL-23 induced IL-17 and limited IL-2 production, whereas T follicular helper and double negative (DN) T cells significantly expanded...
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645307/aberrant-intestinal-microbiota-due-to-il-1-receptor-antagonist-deficiency-promotes-il-17-and-tlr4-dependent-arthritis
#11
Rebecca Rogier, Thomas H A Ederveen, Jos Boekhorst, Harm Wopereis, Jose U Scher, Julia Manasson, Sanne J C M Frambach, Jan Knol, Johan Garssen, Peter M van der Kraan, Marije I Koenders, Wim B van den Berg, Sacha A F T van Hijum, Shahla Abdollahi-Roodsaz
BACKGROUND: Perturbation of commensal intestinal microbiota has been associated with several autoimmune diseases. Mice deficient in interleukin-1 receptor antagonist (Il1rn (-/-) mice) spontaneously develop autoimmune arthritis and are susceptible to other autoimmune diseases such as psoriasis, diabetes, and encephalomyelitis; however, the mechanisms of increased susceptibility to these autoimmune phenotypes are poorly understood. We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) in regulation of commensal intestinal microbiota, and assessed the involvement of microbiota subsets and innate and adaptive mucosal immune responses that underlie the development of spontaneous arthritis in Il1rn (-/-) mice...
June 23, 2017: Microbiome
https://www.readbyqxmd.com/read/28619539/systemic-immunological-changes-in-patients-with-distinct-clinical-outcomes-during-mycobacterium-tuberculosis-infection
#12
Tatiane Figueiredo Morais-Papini, Jordana Grazziela Alves Coelho-Dos-Reis, Ana Paula Barbosa Wendling, Lis Ribeiro do Vale Antonelli, Pryscilla Fanini Wowk, Vânia Luiza Deperon Bonato, Valéria Maria Augusto, Silvana Elói-Santos, Olindo Assis Martins-Filho, Cláudia Martins Carneiro, Andréa Teixeira-Carvalho
BACKGROUND: The lung lesions in an individual infected with tuberculosis (TB) are surprisingly variable and independent of each other. However, there is no circulating biomarker yet able to segregate patients according to the extent of lung lesions. MATERIALS AND METHODS: In this study, the phenotypic and functional profile of leukocytes of patients with active pulmonary tuberculosis (TB) and controls (CO) were fully scrutinized by immunophenotyping assays and in vitro short-term whole blood culture...
May 26, 2017: Immunobiology
https://www.readbyqxmd.com/read/28615106/-enhanced-ilc2-activity-contributes-to-metabolic-syndrome-multicomponent-aggregation-state-in-patients-with-type-2-diabetic-nephropathy
#13
Ping Lu, Yunyun Xu, Zhaoliang Su, Huaxi Xu
Objective To study the relationship between the activity of group II innate lymphoid cells (ILC2) in maintenance hemodialysis patients with type 2 diabetic nephropathy (DN) and metabolic syndrome (MS) multicomponent aggregation state. Methods The study enrolled 30 DN patients of stable condition treated with maintenance hemodialysis over 3 months, 30 newly diagnosed untreated type 2 diabetes patients and 30 healthy volunteers as controls. Real-time quantitative PCR (qRT-PCR) was used to detect the mRNA expression levels of retinoic acid receptor-related orphan receptor α (RORα), interleukin 17 receptor B (IL-17RB), IL-33 receptor T1/ST2, IL-5 and IL-13 in peripheral blood mononuclear cells (PBMCs)...
June 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28612730/-innate-lymphoid-cells
#14
Adeline Crinier, Charlotte Viant, Mathilde Girard-Madoux, Éric Vivier
Innate Lymphoid Cells (ILC) are tissue-resident effector lymphocytes that differ from the B and T lymphocytes subsets since they lack specific antigen receptors derived from gene rearrangements. They can be divided into two groups, cytotoxic ILC (NK cells) which are dependent on the transcription factors Eomes and T-bet and produce IFN-γ, and helper-like ILC (ILC1, ILC2, ILC3) which are dependent on T-bet, GATA-3 or RORγT and produce IFN-γ, IL-5/IL-13 or IL-17/IL-22 respectively. Although they were described recently, ILC are the subject of a large number of studies that characterize their role as one of the first effectors of the innate immune response as well as in the development of a wide number of inflammatory disorders...
May 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28607111/a-distinct-inhibitory-function-for-mir-18a-in-th17-cell-differentiation
#15
Misty M Montoya, Julia Maul, Priti B Singh, Heather H Pua, Frank Dahlström, Nanyan Wu, Xiaozhu Huang, K Mark Ansel, Dirk Baumjohann
Th17 cell responses orchestrate immunity against extracellular pathogens but also underlie autoimmune disease pathogenesis. In this study, we uncovered a distinct and critical role for miR-18a in limiting Th17 cell differentiation. miR-18a was the most dynamically upregulated microRNA of the miR-17-92 cluster in activated T cells. miR-18a deficiency enhanced CCR6(+) RAR-related orphan receptor (ROR)γt(+) Th17 cell differentiation in vitro and increased the number of tissue Th17 cells expressing CCR6, RORγt, and IL-17A in airway inflammation models in vivo...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28604704/thermoneutral-housing-exacerbates-nonalcoholic-fatty-liver-disease-in-mice-and-allows-for-sex-independent-disease-modeling
#16
Daniel A Giles, Maria E Moreno-Fernandez, Traci E Stankiewicz, Simon Graspeuntner, Monica Cappelletti, David Wu, Rajib Mukherjee, Calvin C Chan, Matthew J Lawson, Jared Klarquist, Annika Sünderhauf, Samir Softic, C Ronald Kahn, Kerstin Stemmer, Yoichiro Iwakura, Bruce J Aronow, Rebekah Karns, Kris A Steinbrecher, Christopher L Karp, Rachel Sheridan, Shiva K Shanmukhappa, Damien Reynaud, David B Haslam, Christian Sina, Jan Rupp, Simon P Hogan, Senad Divanovic
Nonalcoholic fatty liver disease (NAFLD), a common prelude to cirrhosis and hepatocellular carcinoma, is the most common chronic liver disease worldwide. Defining the molecular mechanisms underlying the pathogenesis of NAFLD has been hampered by a lack of animal models that closely recapitulate the severe end of the disease spectrum in humans, including bridging hepatic fibrosis. Here we demonstrate that a novel experimental model employing thermoneutral housing, as opposed to standard housing, resulted in lower stress-driven production of corticosterone, augmented mouse proinflammatory immune responses and markedly exacerbated high-fat diet (HFD)-induced NAFLD pathogenesis...
July 2017: Nature Medicine
https://www.readbyqxmd.com/read/28599652/regulatory-t-cells-in-multiple-sclerosis-and-myasthenia-gravis
#17
REVIEW
K M Danikowski, S Jayaraman, B S Prabhakar
Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs)...
June 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28591933/possible-involvement-of-ccr7-pd-1-follicular-helper-t-cell-subset-in-the-pathogenesis-of-autoimmune-hepatitis
#18
Naruhiro Kimura, Satoshi Yamagiwa, Tomoyuki Sugano, Toru Setsu, Kentaro Tominaga, Hiroteru Kamimura, Masaaki Takamura, Shuji Terai
BACKGROUND AND AIM: Recent studies have demonstrated that B cells and follicular helper T (Tfh) cells, which are central regulators of humoral immune response, contribute to the development and progression of autoimmune diseases. Because Tfh cells can be divided into several subsets with distinct functional properties, this study aimed to examine the roles of different subsets of circulating Tfh cells in the immune pathogenesis of autoimmune hepatitis (AIH). METHODS: Thirty-five patients with AIH, 28 patients with primary biliary cholangitis, 24 patients with chronic hepatitis B (CHB), and 44 health controls (HC) were enrolled...
June 7, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28591258/immune-development-in-hiv-exposed-uninfected-children-born-to-hiv-infected-women
#19
Maristela Miyamoto, Aída F T B Gouvêa, Erika Ono, Regina Célia M Succi, Savita Pahwa, Maria Isabel de Moraes-Pinto
Immunological and clinical findings suggestive of some immune dysfunction have been reported among HIV-exposed uninfected (HEU) children and adolescents. Whether these defects are persistent or transitory is still unknown. HEU pediatric population at birth, 12 months, 6-12 years were evaluated in comparison to healthy age-matched HIV-unexposed controls. Plasma levels of LPS, sCD14, cytokines, lymphocyte immunophenotyping and T-cell receptor excision circles (TREC) were assessed. HEU and controls had similar LPS levels, which remained low from birth to 6-12 years; for plasma sCD14, IL-2, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17, IFN-γ, TNF-α, G-CSF, GM-CSF and MCP-1, which increased from birth to 12 months and then decreased at 6-12 years; and for TREC/106 PBMC at birth in HEU and controls...
June 1, 2017: Revista do Instituto de Medicina Tropical de São Paulo
https://www.readbyqxmd.com/read/28546429/structural-studies-unravel-the-active-conformation-of-apo-ror%C3%AE-t-nuclear-receptor-and-a-common-inverse-agonism-of-two-diverse-classes-of-ror%C3%AE-t-inhibitors
#20
COMPARATIVE STUDY
Xiang Li, Marie Anderson, Delphine Collin, Ingo Muegge, John Wan, Debra Brennan, Stanley Kugler, Donna Terenzio, Charles Kennedy, Siqi Lin, Mark E Labadia, Brian Cook, Robert Hughes, Neil A Farrow
The nuclear receptor retinoid acid receptor-related orphan receptor γt (RORγt) is a master regulator of the Th17/IL-17 pathway that plays crucial roles in the pathogenesis of autoimmunity. RORγt has recently emerged as a highly promising target for treatment of a number of autoimmune diseases. Through high-throughput screening, we previously identified several classes of inverse agonists for RORγt. Here, we report the crystal structures for the ligand-binding domain of RORγt in both apo and ligand-bound states...
July 14, 2017: Journal of Biological Chemistry
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